Comprehensive Physiology Wiley Online Library

Modulation of Electrical Properties by Ions, Hormones, and Drugs

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Effects of Electrolytes
1.1 Potassium Ions
1.2 Sodium Ions
1.3 Calcium and Other Divalent Cations
1.4 Chloride Ions
2 Effects of pH and Physical Factors
2.1 pH
2.2 Temperature
2.3 Stretch and Osmotic Pressure
3 Effects of Neurohormones and Their Receptor Stimulations
3.1 Adrenoceptor Agonists and Adrenergic Receptor Stimulation
3.2 Cholinergic Agonists and Cholinergic Receptor Stimulation
4 Effects of Circulatory Hormones and Autocrine/Paracrine Substances
4.1 Thyroid Hormones and Thyroid States
4.2 Insulin and Diabetes Mellitus
4.3 Effects of Adenosine and Adenine Nucleotides Through Purinergic Receptor Stimulation
4.4 Histamine and Histamine H2 Receptor Stimulation
4.5 Angiotensin II and Angiotensin Receptor Stimulation
4.6 Arginine Vasopressin and Vasopressinergic Receptor Stimulation
4.7 Endothelins
4.8 Atrial Natriuretic Peptide
4.9 Nitric Oxide
5 Effects of Drugs
5.1 Digitalis Glucosides
5.2 Potassium Channel Openers
Figure 1. Figure 1.

Effects of increasing [K+]o on action potentials and background membrane currents in atrial and ventricular myocytes. Action potentials and isochronal (5 s) current‐voltage relationships at [K+]o = 6 mM (filled circles) and 11 mM (open circles) in an atrial myocyte (A) and a ventricular myocyte (B) are shown. While action potential and the current‐voltage relationship were not much changed in A with increasing [K+]o from 6 to 11 mM, shortened action potential duration and a shift of I‐V relationship with crossover were evident in B. Tetrodotoxin (3 × 10−5 M) present throughout. In each cell, the holding potential was −50 mV. Vertical calibrations for insets in A and B are 20 mV; horizontal calibration is 50 msec for A and 100 ms for B.

Reproduced from Figure 11 in reference , with permission
Figure 2. Figure 2.

Activation of HERG current by extracellular K+ A–C: Currents elicited by 4 sec pulses to test potentials ranging from −50 to +20 mV in an oocyte bathed in modified ND96 solution containing 10 mM KCI (A) or 2 mM KCI (B) or 5 min after switching to ND96 solution with no added KCI (C). D: I‐V relationship for currents shown in A–C. E: HERG current amplitude varies as a function of [K+]o. Currents were measured at a test potential of +20 mV (n = 4–6). The solid line is a linear fit to data (IHERG = 189 + 37.5 [K+]o). Note that this relationship at lower and higher [K+]o would not be expected to be a linear function of [K+]o.

Reproduced from Figure 4 in reference with permission
Figure 3. Figure 3.

[Ca2+]i induced potentiation and inhibition in the L‐type Ca2+ channel activity A: control; B: about 10 min after the bath solution was switched to Ca2+‐containing solution. Top panels show R340/380 indicating [Ca2+]i and bottom panels show NPO of the L‐type Ca2+ channel activity during each depolarizing pulse to O mV delivered at 1 Hz. C: unitary current records during the period indicated by bars in A and B. With increasing [Ca2+]i, channel activity was initially increased as shown in B‐b and C‐b. With further increase in [Ca2+]i above F340/380 ratio = 1.0, channel activity was now quickly inhibited (B‐c and C‐c). However, inhibitory effect was transient and with fluctuation of [Ca2+]i, channel activity was restored to the level which was still higher than the control B‐d and C‐d).

Reproduced from Figure 11 in reference with permission
Figure 4. Figure 4.

Activation of ICl.Ca in different intracellular Ca2+ concentrations. A: ICl.Ca measured as 4,4′‐ddisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS)‐sensitive current traces at four different concentrations of Ca2+ in the pipette. The pipette solution contained 1 nM Ca2+ in a, 10 nM Ca2+ in b, 0.1 μ M Ca2+ in c, and 1 μM free Ca2+ in d. All experiments were done in the presence of 4 mM 4‐AP. Depolarizing pulses were applied from −60 mV to test potentials indicated to the left of each trace. B: current‐voltage relations of ICl.Ca. Data represent means ± S.E.M. •, 1 μM free Ca2+; ◯, 0.1 μM Ca2+; ▾, 10 nM Ca2+. Currents were normalized by dividing with total cell capacity.

Reproduced from Figure 6 in reference with permission
Figure 5. Figure 5.

Current changes in response to inflation and deflation of sinoatrial node cell by applying positive and negative pressure through the recording electrode. A: chart record (10 mm/min) of current changes in response to the ramp clamp. The current traces indicated by a‐c are shown in B. The duration of inflation and deflation are indicated above the current trace. The pipette solution contained 24 mM C1 and the reversal potential for C1 (Ecl) was calculated to be −49 mV. The reversal potential of the stretch‐activated current was −48 mV (arrow in B), suggesting that the current activated in response to inflation of the cell is C1 elective.

Reproduced from Figure 2 in reference , with permission
Figure 6. Figure 6.

Effect of isoprenaline on the single Ca2+ channel currents. A: control; B: in the presence of 100 nM isoprenaline; C: after wash‐out of the drug. Depolarizing steps of 400 ms to −10 mV were applied repetitively from a holding potential (HP) of −80 mV at 2 Hz; 50 mM Ba2+ in the pipette. The number of steps was about 500 in each solution. a: typical current sweeps obtained after leakage current subtraction are given in the order of stimulation. Filtered at 1.5 kHz. b: the bottom traces: mean currents obtained by averaging the simulated openings from the total sweeps, including blank sweeps, on the same arbitrary scale. The ratio of the number of current‐containing sweeps to the total number of sweeps (availability) is given above each mean current.

Reproduced from Figure 1 in reference , with permission
Figure 7. Figure 7.

Effects of α1‐adrenergic stimulation on Ito single‐channel events. (I): A and B show a series of ten consecutive sweeps of single‐channel openings recorded under control conditions (A) and during bath exposure of the cell to 0.2 mM methoxamine (B). Ito single‐channel events were recorded following formation of the cell‐attached seal (about 100 GΩ); the patch membrane was held at −50 mV relative to the cell resting potential. Channel openings were elicited by 350 ms depolarizing pulses (150 mV) at a rate of 0.1 Hz. To remove the capacitative and leak currents from the single‐channel records, depolarizing pulses were applied at a rate of 2 Hz, and a total of ten to fifteen blank sweeps were averaged. This averaged record was then subtracted from the individual sweeps. C and D show the effect of methoxamine on the burst open probability of single Ito, channels (same patch as A and B). The burst open probability was determined by dividing the summed durations of individual openings present with a burst by the total duration of the given burst. A total of seventy to eighty bursts were recorded under control conditions (C) and in the presence of 0.2 mM methoxamine (D). (II): Effect of methoxamine on an ensemble average of the single‐channel events underlying Ito, from a cell‐attached patch containing several channels. Groups of thirty records were averaged before (C), during application of 0.2 mM methoxamine to the bath (M), and after wash‐out of methoxamine (W) from the bath. Depolarizing steps (+200 mV with respect to the cell resting potential; patch holding potential, −50 mV with respect to rest) were applied at a rate of 0.1 Hz.

Reproduced from Figures and in reference , with permission
Figure 8. Figure 8.

Activation of K+ channel by Ado and ACh requires intracellular GTP and blocked by IAP (islet‐activating protein or pertussis toxin). A: The cells were bathed in the internal solution. The concentration of agonists and the patch membrane potential are indicated at each current trace. At the arrow in each trace, the patch was excised from the cell, yielding the “inside‐out” patch. Activation of the channel was blocked in the “inside‐out” patches. During the period shown by the bar above each current trace, internal solution containing GTP 100 μM was perfused. Activation of the channel resumed abruptly by addition of GTP into the bath solution. B: The same patches as those in A. With GTP 100 μM present in the intracellular side of the membrane, channels remained activated. The A (active) protomer of IAP with NAD 1 mM was added in the internal solution containing GTP during the period indicated by the bar above each trace. Channel activation was gradually blocked by IAP within 1–3 min. The blocking effect of IAP was irreversible. When the A protomer was perfused in the absence of NAD, the activation of the channel was not blocked.

Reproduced from Figure 9 in reference with permission
Figure 9. Figure 9.

Effects of ACh on SA node cells. Left: Effects of different ACh concentrations on the rate of spontaneous activity in an SA node myocyte. Activity was recorded in control Tyrode's solution (c) and during superfusion with ACh 0.01 μM (top) and 1 μM (bottom), as indicated. Right: Separation of the effects of ACh on Ii and IK.ACH. Two‐pulse protocols were applied every 3 sec during superfusion with various doses of ACh. The myocyte was superfused with normal Tyrode's solution (O, control) and with Tyrode's containing 0.01 (*), 0.1 (+), and 1 μM (x) ACh. In each case ACh superfusion was maintained until a steady‐state effect was achieved, typically 20 sec, and was followed by an appropriate washout period.

Reproduced from Figures and in reference , with permission
Figure 10. Figure 10.

Effect of isoproterenol (ISO), adenosine (Ado), and theophylline (Theo) on single‐channel Ca2+ current. A: Control; B: 100 nM ISO; C: 0.1 mM Ado and ISO; D: ISO, Ado, and 0.1 mM Theo. Traces labeled a are ten consecutive sweeps in order of depolarization sequence. Artifacts produced by capacitive transients were erased at the intervals indicated by the two dots. Traces labeled b are mean currents (m.c.) from all traces, including blanks. Mean currents were obtained by averaging the idealized openings and are shown on a constant arbitrary scale. About 1,000 times of 100 msec depolarization steps from the resting potential (R.P.) to R.P. +90 mV were applied repetitively at 2 Hz in each solution. Cutoff frequency was 1.5 kHz. Pipette solution contained 100 mM Ba2+, T.P.=test potential, H.P. = holding potential; Ps,=ratio of the number of channel currents containing sweeps to total number of sweeps.

Reproduced from Figure 1 in reference , with permission
Figure 11. Figure 11.

Desensitization and resensitization of the transient component of current evoked by external ATP. A: Current at — 130 mV during two applications of 200 μM ATP separated by 30 sec. While a transient current was lost in the second exposure to ATP due to desensitization, a maintained current response after the transient current was similarly evoked in the second exposure as in the first application. B: Time course of recovery from desensitization in two cells. In each trial, an initial 15‐sec application of 200 μM ATP was followed by a variable recovery time, and the extent of recovery was tested with a second application of ATP. Cells were allowed to recover for 6 min between trials. Filled circles: cell C78E. Open circles: cell C79B.

Reproduced from Figure 3 in reference with permission
Figure 12. Figure 12.

Effect of endothelin‐1 (ET‐1) on the T‐type Ca2+ current ICa.T). A: A series of ICa.T were elicited by voltage steps to —30 mV in the control condition, 20 min after the addition of 10 nMET‐1, and 10 min after removal of ET‐1, and the tracings are superimposed. B: Peak current density‐voltage relations were plotted for ICa.T in the control condition (closed circles), 20 min after the addition of 10 nM ET‐1 (open reversed triangles), and 10 mins after the removal of ET‐1 (open squares) obtained from 11 cells. *P<0.05 and # P<0.01 for the control condition vs. ET‐1 and for ET‐1 vs. washout of ET‐1.

Reproduced from Figure 5 in reference with permission
Figure 13. Figure 13.

The effect of strophanthidin on action potential and ICa when myocytes are impaled with BAPTA‐filled microelectrodes to increase Ca2+i buffering. A: The effect on the action potential of exposure to two different concentrations of strophanthidin. B: individual action potentials recorded at the times indicated in A. C: ICa recorded with the two‐pulse protocol before and at the end of strophanthidin exposure. D: The time course of the change in ICa during strophanthidin exposure and recovery.

Reproduced from Figure 8 in reference , with permission
Figure 14. Figure 14.

Effects of pinacidil on activation of ATP‐sensitive K+ channel currents recorded from an inside‐out patch membrane. A: Voltage‐dependent activation. Membrane potential [Vm (mV)] is indicated at the left of each trace. Left panel shows records taken during the control experiment with 0.5 mM ATP in the internal solution; right panel presents those with a solution containing 30 μM pinacidil and 2 mM ATP. The current direction is outward at positive voltages and inward at negative voltages. B a: Amplitude histograms (top panel) of the single‐channel current at Vm = −80 mV (left panel) and Vm = + 80 mV (right panel) obtained using the control solution containing 0.5 mM ATP. B b: Amplitude histograms (bottom panel) of the single‐channel current at Vm = 80 mV (left panel and Vm = +80 mV (right panel) obtained using solution containing 30 μM pinacidil and 2 mM ATP. Note that the current amplitude of the single channel is not changed by pinacidil. C: Current‐voltage relationship (I‐V) and the effect of pinacidil. Pinacidil does not change the conductance of this channel current.

Reproduced from Figure 2 in reference , with permission
Figure 15. Figure 15.

Concentration‐dependent effects of nicorandil on the SUR2A/Kir6.2 and SUR2B/Kir6.2 channels. Concentration‐dependent effects of nicorandil on the whole‐cell current of the SUR2A/Kir6.2 (a) and SUR2B/Kir6.2 channels (b) at −30 mV with 5.4 mM external K+. Arrowheads indicate the zero current level. The perfusion protocol is indicated above, c: Relationship between the concentration of nicorandil and the whole‐cell current of the SUR2A/Kir6.2 (open circles) and SUR2B/Kir6.2 channels (solid circles). The current amplitude induced by each concentration of nicorandil was normalized to the pinacidil (100 μM)‐induced current in the same cell. Each symbol and vertical lines indicate the mean and SE, respectively. The number of observations at each point was 5. The line is the fit of the data with the equation.Where the relative current is the current normalized to that induced by 100 μM pinacidil in the same cell; A is the maximum relative current induced by nicorandil; and [Nicorandil], the concentration of nicorandil. The values of A, K and nH were 1.05, 9.2 μM and 1.30, respectively.

Reproduced from Figure 3 in reference with permission


Figure 1.

Effects of increasing [K+]o on action potentials and background membrane currents in atrial and ventricular myocytes. Action potentials and isochronal (5 s) current‐voltage relationships at [K+]o = 6 mM (filled circles) and 11 mM (open circles) in an atrial myocyte (A) and a ventricular myocyte (B) are shown. While action potential and the current‐voltage relationship were not much changed in A with increasing [K+]o from 6 to 11 mM, shortened action potential duration and a shift of I‐V relationship with crossover were evident in B. Tetrodotoxin (3 × 10−5 M) present throughout. In each cell, the holding potential was −50 mV. Vertical calibrations for insets in A and B are 20 mV; horizontal calibration is 50 msec for A and 100 ms for B.

Reproduced from Figure 11 in reference , with permission


Figure 2.

Activation of HERG current by extracellular K+ A–C: Currents elicited by 4 sec pulses to test potentials ranging from −50 to +20 mV in an oocyte bathed in modified ND96 solution containing 10 mM KCI (A) or 2 mM KCI (B) or 5 min after switching to ND96 solution with no added KCI (C). D: I‐V relationship for currents shown in A–C. E: HERG current amplitude varies as a function of [K+]o. Currents were measured at a test potential of +20 mV (n = 4–6). The solid line is a linear fit to data (IHERG = 189 + 37.5 [K+]o). Note that this relationship at lower and higher [K+]o would not be expected to be a linear function of [K+]o.

Reproduced from Figure 4 in reference with permission


Figure 3.

[Ca2+]i induced potentiation and inhibition in the L‐type Ca2+ channel activity A: control; B: about 10 min after the bath solution was switched to Ca2+‐containing solution. Top panels show R340/380 indicating [Ca2+]i and bottom panels show NPO of the L‐type Ca2+ channel activity during each depolarizing pulse to O mV delivered at 1 Hz. C: unitary current records during the period indicated by bars in A and B. With increasing [Ca2+]i, channel activity was initially increased as shown in B‐b and C‐b. With further increase in [Ca2+]i above F340/380 ratio = 1.0, channel activity was now quickly inhibited (B‐c and C‐c). However, inhibitory effect was transient and with fluctuation of [Ca2+]i, channel activity was restored to the level which was still higher than the control B‐d and C‐d).

Reproduced from Figure 11 in reference with permission


Figure 4.

Activation of ICl.Ca in different intracellular Ca2+ concentrations. A: ICl.Ca measured as 4,4′‐ddisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS)‐sensitive current traces at four different concentrations of Ca2+ in the pipette. The pipette solution contained 1 nM Ca2+ in a, 10 nM Ca2+ in b, 0.1 μ M Ca2+ in c, and 1 μM free Ca2+ in d. All experiments were done in the presence of 4 mM 4‐AP. Depolarizing pulses were applied from −60 mV to test potentials indicated to the left of each trace. B: current‐voltage relations of ICl.Ca. Data represent means ± S.E.M. •, 1 μM free Ca2+; ◯, 0.1 μM Ca2+; ▾, 10 nM Ca2+. Currents were normalized by dividing with total cell capacity.

Reproduced from Figure 6 in reference with permission


Figure 5.

Current changes in response to inflation and deflation of sinoatrial node cell by applying positive and negative pressure through the recording electrode. A: chart record (10 mm/min) of current changes in response to the ramp clamp. The current traces indicated by a‐c are shown in B. The duration of inflation and deflation are indicated above the current trace. The pipette solution contained 24 mM C1 and the reversal potential for C1 (Ecl) was calculated to be −49 mV. The reversal potential of the stretch‐activated current was −48 mV (arrow in B), suggesting that the current activated in response to inflation of the cell is C1 elective.

Reproduced from Figure 2 in reference , with permission


Figure 6.

Effect of isoprenaline on the single Ca2+ channel currents. A: control; B: in the presence of 100 nM isoprenaline; C: after wash‐out of the drug. Depolarizing steps of 400 ms to −10 mV were applied repetitively from a holding potential (HP) of −80 mV at 2 Hz; 50 mM Ba2+ in the pipette. The number of steps was about 500 in each solution. a: typical current sweeps obtained after leakage current subtraction are given in the order of stimulation. Filtered at 1.5 kHz. b: the bottom traces: mean currents obtained by averaging the simulated openings from the total sweeps, including blank sweeps, on the same arbitrary scale. The ratio of the number of current‐containing sweeps to the total number of sweeps (availability) is given above each mean current.

Reproduced from Figure 1 in reference , with permission


Figure 7.

Effects of α1‐adrenergic stimulation on Ito single‐channel events. (I): A and B show a series of ten consecutive sweeps of single‐channel openings recorded under control conditions (A) and during bath exposure of the cell to 0.2 mM methoxamine (B). Ito single‐channel events were recorded following formation of the cell‐attached seal (about 100 GΩ); the patch membrane was held at −50 mV relative to the cell resting potential. Channel openings were elicited by 350 ms depolarizing pulses (150 mV) at a rate of 0.1 Hz. To remove the capacitative and leak currents from the single‐channel records, depolarizing pulses were applied at a rate of 2 Hz, and a total of ten to fifteen blank sweeps were averaged. This averaged record was then subtracted from the individual sweeps. C and D show the effect of methoxamine on the burst open probability of single Ito, channels (same patch as A and B). The burst open probability was determined by dividing the summed durations of individual openings present with a burst by the total duration of the given burst. A total of seventy to eighty bursts were recorded under control conditions (C) and in the presence of 0.2 mM methoxamine (D). (II): Effect of methoxamine on an ensemble average of the single‐channel events underlying Ito, from a cell‐attached patch containing several channels. Groups of thirty records were averaged before (C), during application of 0.2 mM methoxamine to the bath (M), and after wash‐out of methoxamine (W) from the bath. Depolarizing steps (+200 mV with respect to the cell resting potential; patch holding potential, −50 mV with respect to rest) were applied at a rate of 0.1 Hz.

Reproduced from Figures and in reference , with permission


Figure 8.

Activation of K+ channel by Ado and ACh requires intracellular GTP and blocked by IAP (islet‐activating protein or pertussis toxin). A: The cells were bathed in the internal solution. The concentration of agonists and the patch membrane potential are indicated at each current trace. At the arrow in each trace, the patch was excised from the cell, yielding the “inside‐out” patch. Activation of the channel was blocked in the “inside‐out” patches. During the period shown by the bar above each current trace, internal solution containing GTP 100 μM was perfused. Activation of the channel resumed abruptly by addition of GTP into the bath solution. B: The same patches as those in A. With GTP 100 μM present in the intracellular side of the membrane, channels remained activated. The A (active) protomer of IAP with NAD 1 mM was added in the internal solution containing GTP during the period indicated by the bar above each trace. Channel activation was gradually blocked by IAP within 1–3 min. The blocking effect of IAP was irreversible. When the A protomer was perfused in the absence of NAD, the activation of the channel was not blocked.

Reproduced from Figure 9 in reference with permission


Figure 9.

Effects of ACh on SA node cells. Left: Effects of different ACh concentrations on the rate of spontaneous activity in an SA node myocyte. Activity was recorded in control Tyrode's solution (c) and during superfusion with ACh 0.01 μM (top) and 1 μM (bottom), as indicated. Right: Separation of the effects of ACh on Ii and IK.ACH. Two‐pulse protocols were applied every 3 sec during superfusion with various doses of ACh. The myocyte was superfused with normal Tyrode's solution (O, control) and with Tyrode's containing 0.01 (*), 0.1 (+), and 1 μM (x) ACh. In each case ACh superfusion was maintained until a steady‐state effect was achieved, typically 20 sec, and was followed by an appropriate washout period.

Reproduced from Figures and in reference , with permission


Figure 10.

Effect of isoproterenol (ISO), adenosine (Ado), and theophylline (Theo) on single‐channel Ca2+ current. A: Control; B: 100 nM ISO; C: 0.1 mM Ado and ISO; D: ISO, Ado, and 0.1 mM Theo. Traces labeled a are ten consecutive sweeps in order of depolarization sequence. Artifacts produced by capacitive transients were erased at the intervals indicated by the two dots. Traces labeled b are mean currents (m.c.) from all traces, including blanks. Mean currents were obtained by averaging the idealized openings and are shown on a constant arbitrary scale. About 1,000 times of 100 msec depolarization steps from the resting potential (R.P.) to R.P. +90 mV were applied repetitively at 2 Hz in each solution. Cutoff frequency was 1.5 kHz. Pipette solution contained 100 mM Ba2+, T.P.=test potential, H.P. = holding potential; Ps,=ratio of the number of channel currents containing sweeps to total number of sweeps.

Reproduced from Figure 1 in reference , with permission


Figure 11.

Desensitization and resensitization of the transient component of current evoked by external ATP. A: Current at — 130 mV during two applications of 200 μM ATP separated by 30 sec. While a transient current was lost in the second exposure to ATP due to desensitization, a maintained current response after the transient current was similarly evoked in the second exposure as in the first application. B: Time course of recovery from desensitization in two cells. In each trial, an initial 15‐sec application of 200 μM ATP was followed by a variable recovery time, and the extent of recovery was tested with a second application of ATP. Cells were allowed to recover for 6 min between trials. Filled circles: cell C78E. Open circles: cell C79B.

Reproduced from Figure 3 in reference with permission


Figure 12.

Effect of endothelin‐1 (ET‐1) on the T‐type Ca2+ current ICa.T). A: A series of ICa.T were elicited by voltage steps to —30 mV in the control condition, 20 min after the addition of 10 nMET‐1, and 10 min after removal of ET‐1, and the tracings are superimposed. B: Peak current density‐voltage relations were plotted for ICa.T in the control condition (closed circles), 20 min after the addition of 10 nM ET‐1 (open reversed triangles), and 10 mins after the removal of ET‐1 (open squares) obtained from 11 cells. *P<0.05 and # P<0.01 for the control condition vs. ET‐1 and for ET‐1 vs. washout of ET‐1.

Reproduced from Figure 5 in reference with permission


Figure 13.

The effect of strophanthidin on action potential and ICa when myocytes are impaled with BAPTA‐filled microelectrodes to increase Ca2+i buffering. A: The effect on the action potential of exposure to two different concentrations of strophanthidin. B: individual action potentials recorded at the times indicated in A. C: ICa recorded with the two‐pulse protocol before and at the end of strophanthidin exposure. D: The time course of the change in ICa during strophanthidin exposure and recovery.

Reproduced from Figure 8 in reference , with permission


Figure 14.

Effects of pinacidil on activation of ATP‐sensitive K+ channel currents recorded from an inside‐out patch membrane. A: Voltage‐dependent activation. Membrane potential [Vm (mV)] is indicated at the left of each trace. Left panel shows records taken during the control experiment with 0.5 mM ATP in the internal solution; right panel presents those with a solution containing 30 μM pinacidil and 2 mM ATP. The current direction is outward at positive voltages and inward at negative voltages. B a: Amplitude histograms (top panel) of the single‐channel current at Vm = −80 mV (left panel) and Vm = + 80 mV (right panel) obtained using the control solution containing 0.5 mM ATP. B b: Amplitude histograms (bottom panel) of the single‐channel current at Vm = 80 mV (left panel and Vm = +80 mV (right panel) obtained using solution containing 30 μM pinacidil and 2 mM ATP. Note that the current amplitude of the single channel is not changed by pinacidil. C: Current‐voltage relationship (I‐V) and the effect of pinacidil. Pinacidil does not change the conductance of this channel current.

Reproduced from Figure 2 in reference , with permission


Figure 15.

Concentration‐dependent effects of nicorandil on the SUR2A/Kir6.2 and SUR2B/Kir6.2 channels. Concentration‐dependent effects of nicorandil on the whole‐cell current of the SUR2A/Kir6.2 (a) and SUR2B/Kir6.2 channels (b) at −30 mV with 5.4 mM external K+. Arrowheads indicate the zero current level. The perfusion protocol is indicated above, c: Relationship between the concentration of nicorandil and the whole‐cell current of the SUR2A/Kir6.2 (open circles) and SUR2B/Kir6.2 channels (solid circles). The current amplitude induced by each concentration of nicorandil was normalized to the pinacidil (100 μM)‐induced current in the same cell. Each symbol and vertical lines indicate the mean and SE, respectively. The number of observations at each point was 5. The line is the fit of the data with the equation.Where the relative current is the current normalized to that induced by 100 μM pinacidil in the same cell; A is the maximum relative current induced by nicorandil; and [Nicorandil], the concentration of nicorandil. The values of A, K and nH were 1.05, 9.2 μM and 1.30, respectively.

Reproduced from Figure 3 in reference with permission
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Masayasu Hiraoka. Modulation of Electrical Properties by Ions, Hormones, and Drugs. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 595-653. First published in print 2002. doi: 10.1002/cphy.cp020116