Intracellular pH

Cell Physiology > Membrane Physiology > Membrane Transport

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Robert W. Putnam, Albert Roos

10.1002/cphy.cp140109

Source: Supplement 31: Handbook of Physiology, Cell Physiology

Originally published: 1997

Published online: January 2011

Full Article on Wiley Online Library

Abstract
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Abstract

The sections in this article are:

1 Techniques

1.1 pH‐Sensitive Microelectrodes

1.2 pH‐Sensitive Fluorescent Indicators

1.3 Nuclear Magnetic Resonance Spectroscopy

2 Some Observations on Intracellular pH Transients

3 Mechanisms of pH Regulation

3.1 Physicochemical Buffers

3.2 Membrane Transport Systems

3.3 Determinants of Steady‐State pHi

4 Some Cellular Processes Affecting or Affected by pHi

4.1 Metabolism

4.2 Cell‐Cell Coupling: Gap Junctions

4.3 DNA Synthesis and Cell Growth

4.4 Membrane Channels

4.5 Cell‐Volume Regulation

4.6 Mitochondrial H+ Movements

4.7 Cytoskeleton

4.8 Endocytosis/Exocytosis

4.9 Other Cellular Processes

	Figure 1. pH_i transients of a barnacle muscle fiber in CO₂‐free artificial seawater (pH 7.6, room temperature) upon exposure to a solution containing 5% CO₂/50 mM of the same pH, measured with a glass pH‐sensitive microelectrode of the Hinke type 55. Reprinted with the permission of the American Physiological Society. For interpretation of this and the following four figures, see text under SOME OBSERVATIONS ON INTRACELLULAR pH TRANSIENTS
	Figure 2. V_m and pH_i transients in snail neurons in CO₂‐free buffer (pH 7.5, room temperature) upon successive exposures to three different levels of at the same pH of 7.5. V_m was measured with a standard 3 M KCl‐filled glass microelectrode and pH_i with a glass pH‐sensitive microelectrode of the Thomas type. Modified from Thomas 434. Reprinted with the permission of the Journal of Physiology (London). The original pH_i trace has been refined by inverting the ordinate to make the figure intelligible to New World scientists
	Figure 3. V_m and pH_i transients in semitendinosus muscle fibers from the frog, Rana pipiens, in CO₂‐free HEPES buffer (pH 7.35, room temperature), upon exposure to a solution containing 5% CO₂/24 mM of the same pH. V_m was measured with a standard 3M KCl‐filled glass microelectrode and pH_i with a glass pH‐sensitive microelectrode of the Thomas type. Fibers were in solutions containing 2.5 mM K⁺ either with (A) or without (B) external Na⁺ (Na⁺ completely substituted by NMDG) 1. Reprinted with the permission of the American Physiological Society
	Figure 4. V_m and pH_i transients in a guinea‐pig smooth muscle cell from vas deferens. The cells were first exposed to 3% CO₂/14 mM , then to CO₂‐free solution, and finally again to 3% CO₂ solution. Temperature was 35°C. V_m and pH_i were measured with a double‐barreled microelectrode using a reference liquid ion exchanger for the V_m barrel and a pH‐sensitive liquid ion exchanger for the pH barrel. Modified from Aickin 6. Reprinted with the permission of the Journal of Physiology (London)
	Figure 5. pH_i transients in cultured monolayers of primary rat astrocytes upon exposure to a CO₂‐free solution containing 30 mM NH₄Cl, measured with the pH‐sensitive fluorescent dye BCECF. The pH_o was 7.4 throughout; temperature was 37°C. The superimposed pH_i courses are shown when, upon NH₄Cl removal, the solution was temporarily changed either to an Na⁺‐free solution (substitution by N‐methyl‐D‐glucamine), or to one containing 1 mM amiloride Shrode and Putnam, unpublished observations
	Figure 6. Comparison of the buffering power, β, under closed and open conditions of each of two monovalent buffers; a weak acid, HA/A⁻, and a weak base, B/BH⁺. “Closed” means fixed total buffer concentration, [C]. “Open” means fixed concentration of the uncharged partner, [HA] or [B]. For simplicity, the buffers are assumed to have the same pK′ of 7.0 and, at pH = pK′, the same [C], 10 mM, both when open and closed. The β‐pH relationship of the two closed buffers is the same; β is maximal at pH = pK′, namely 5.76 mM/pH unit (that is, 0.576[C]). For the open buffers, β at pH = pK′ is twice this value, or 11.52 mM/pH unit (that is, 2.303[A⁻] or 2.303[HB⁺]), but their β‐pH relationships have no maximum. Instead, β increases exponentially with pH in the case of the acid, and decreases exponentially with pH in the case of the base. See text under Physicochemical Buffers for further discussion.
	Figure 7. Models of three different types of cotransporters. A. The 3 base equivalents:1 Na⁺ electrogenic cotransporter present in rabbit renal proximal tubule cells. The transport involves the efflux of 1 and 1 along with a single Na⁺. B. The 2 base equivalents:1 Na⁺ electrogenic cotransporter. It is not certain whether this mechanism in frog retinal pigment epithelium involves the influx of each Na⁺ with 2 (Model a) or 1 (Model b). C. The 1 :1 Na⁺ electroneutral cotransporter in sheep cardiac Purkinje fibers. It involves the influx of a single per Na⁺.
	Figure 8. Dependence of rate of acid efflux, JH (product of rate of pH_i recovery and buffering power), upon pH_i during pH_i recovery from cell acidification in cultured BC3H‐1 myocytes. •, Acid efflux mediated by the Na⁺/H⁺ exchanger; ○, acid efflux mediated by the Na⁺‐dependent exchanger. The values for the Na⁺/H⁺ exchanger were collected in the absence of in cells acidified to varying degrees (pH_i 5.95 to 7.15) after exposure to 15 mM NH₄Cl (for example, see Fig. 5). The rate of recovery was determined from the slope of the pH vs. time trace during the first minute of pH_i recovery from acidification and has been shown to be due to Na⁺/H⁺ exchange only 339. The values for the Na⁺‐dependent exchanger were collected in the presence of 5% CO₂/24 mM and 1 mM amiloride (to inhibit Na⁺/H⁺ exchange). These cells were acidified to varying degrees (pH_i 6.15 to 7.25) after exposure to either 15 or 30 mM NH₄Cl. Again, the rate of recovery was determined from the slope of the pH vs. time trace during the first minute of pH_i recovery from acidification. The recovery under these conditions has been shown to be entirely due to Na⁺‐dependent exchange 339. Each experiment yielded only one recovery value. Each point represents the mean ± 1 standard error of from 3–8 separate experiments. The curves were fitted by eye. Note that the activity of the Na⁺‐dependent exchanger predominates in the pH_i range of 7.2 to about 6.7. Below 6.6, the Na⁺/H⁺ exchanger increasingly predominates Putnam, unpublished observations
	Figure 9. Effect on cell acid‐base balance of removal of 5 mmoles of per liter cytosolic water (in exchange for 5 mmoles of Cl⁻). Point A represents initial conditions: pH_i = 7.3, []_i = 16 mM, PCO₂ = 33 mm Hg. Point B represents the hypothetical case in which the reduction of pH_i resulting from removal is canceled by simultaneous reduction of PCO₂: pH_i = 7.3, []_i = 11 mM, PCO₂ = 23 mm Hg. Point C represents the actual conditions when is removed at unchanged PCO₂: pH_i = 7.2, []_i = 13 mM, PCO₂ = 33 mm Hg. The iso‐PCO₂ curves are constructed taking the “overall” pK₁′ of CO₂ as 6.1 and CO₂ solubility as 0.03 mmole 1⁻¹ mm Hg⁻¹. The slope of the parallel lines is a measure of the non‐ buffering power, which remains the same in the three conditions at an assumed value of 20 mM per pH unit. For details, see text.

Figure 1.

pH_i transients of a barnacle muscle fiber in CO₂‐free artificial seawater (pH 7.6, room temperature) upon exposure to a solution containing 5% CO₂/50 mM of the same pH, measured with a glass pH‐sensitive microelectrode of the Hinke type 55.

Reprinted with the permission of the American Physiological Society. For interpretation of this and the following four figures, see text under SOME OBSERVATIONS ON INTRACELLULAR pH TRANSIENTS

Figure 2.

V_m and pH_i transients in snail neurons in CO₂‐free buffer (pH 7.5, room temperature) upon successive exposures to three different levels of at the same pH of 7.5. V_m was measured with a standard 3 M KCl‐filled glass microelectrode and pH_i with a glass pH‐sensitive microelectrode of the Thomas type. Modified from Thomas 434.

Reprinted with the permission of the Journal of Physiology (London). The original pH_i trace has been refined by inverting the ordinate to make the figure intelligible to New World scientists

Figure 3.

V_m and pH_i transients in semitendinosus muscle fibers from the frog, Rana pipiens, in CO₂‐free HEPES buffer (pH 7.35, room temperature), upon exposure to a solution containing 5% CO₂/24 mM of the same pH. V_m was measured with a standard 3M KCl‐filled glass microelectrode and pH_i with a glass pH‐sensitive microelectrode of the Thomas type. Fibers were in solutions containing 2.5 mM K⁺ either with (A) or without (B) external Na⁺ (Na⁺ completely substituted by NMDG) 1.

Reprinted with the permission of the American Physiological Society

Figure 4.

V_m and pH_i transients in a guinea‐pig smooth muscle cell from vas deferens. The cells were first exposed to 3% CO₂/14 mM , then to CO₂‐free solution, and finally again to 3% CO₂ solution. Temperature was 35°C. V_m and pH_i were measured with a double‐barreled microelectrode using a reference liquid ion exchanger for the V_m barrel and a pH‐sensitive liquid ion exchanger for the pH barrel. Modified from Aickin 6.

Reprinted with the permission of the Journal of Physiology (London)

Figure 5.

pH_i transients in cultured monolayers of primary rat astrocytes upon exposure to a CO₂‐free solution containing 30 mM NH₄Cl, measured with the pH‐sensitive fluorescent dye BCECF. The pH_o was 7.4 throughout; temperature was 37°C. The superimposed pH_i courses are shown when, upon NH₄Cl removal, the solution was temporarily changed either to an Na⁺‐free solution (substitution by N‐methyl‐D‐glucamine), or to one containing 1 mM amiloride

Shrode and Putnam, unpublished observations

Figure 6.

Comparison of the buffering power, β, under closed and open conditions of each of two monovalent buffers; a weak acid, HA/A⁻, and a weak base, B/BH⁺. “Closed” means fixed total buffer concentration, [C]. “Open” means fixed concentration of the uncharged partner, [HA] or [B]. For simplicity, the buffers are assumed to have the same pK′ of 7.0 and, at pH = pK′, the same [C], 10 mM, both when open and closed. The β‐pH relationship of the two closed buffers is the same; β is maximal at pH = pK′, namely 5.76 mM/pH unit (that is, 0.576[C]). For the open buffers, β at pH = pK′ is twice this value, or 11.52 mM/pH unit (that is, 2.303[A⁻] or 2.303[HB⁺]), but their β‐pH relationships have no maximum. Instead, β increases exponentially with pH in the case of the acid, and decreases exponentially with pH in the case of the base. See text under Physicochemical Buffers for further discussion.

Figure 7.

Models of three different types of cotransporters. A. The 3 base equivalents:1 Na⁺ electrogenic cotransporter present in rabbit renal proximal tubule cells. The transport involves the efflux of 1 and 1 along with a single Na⁺. B. The 2 base equivalents:1 Na⁺ electrogenic cotransporter. It is not certain whether this mechanism in frog retinal pigment epithelium involves the influx of each Na⁺ with 2 (Model a) or 1 (Model b). C. The 1 :1 Na⁺ electroneutral cotransporter in sheep cardiac Purkinje fibers. It involves the influx of a single per Na⁺.

Figure 8.

Dependence of rate of acid efflux, JH (product of rate of pH_i recovery and buffering power), upon pH_i during pH_i recovery from cell acidification in cultured BC3H‐1 myocytes. •, Acid efflux mediated by the Na⁺/H⁺ exchanger; ○, acid efflux mediated by the Na⁺‐dependent exchanger. The values for the Na⁺/H⁺ exchanger were collected in the absence of in cells acidified to varying degrees (pH_i 5.95 to 7.15) after exposure to 15 mM NH₄Cl (for example, see Fig. 5). The rate of recovery was determined from the slope of the pH vs. time trace during the first minute of pH_i recovery from acidification and has been shown to be due to Na⁺/H⁺ exchange only 339. The values for the Na⁺‐dependent exchanger were collected in the presence of 5% CO₂/24 mM and 1 mM amiloride (to inhibit Na⁺/H⁺ exchange). These cells were acidified to varying degrees (pH_i 6.15 to 7.25) after exposure to either 15 or 30 mM NH₄Cl. Again, the rate of recovery was determined from the slope of the pH vs. time trace during the first minute of pH_i recovery from acidification. The recovery under these conditions has been shown to be entirely due to Na⁺‐dependent exchange 339. Each experiment yielded only one recovery value. Each point represents the mean ± 1 standard error of from 3–8 separate experiments. The curves were fitted by eye. Note that the activity of the Na⁺‐dependent exchanger predominates in the pH_i range of 7.2 to about 6.7. Below 6.6, the Na⁺/H⁺ exchanger increasingly predominates

Putnam, unpublished observations

Figure 9.

Effect on cell acid‐base balance of removal of 5 mmoles of per liter cytosolic water (in exchange for 5 mmoles of Cl⁻). Point A represents initial conditions: pH_i = 7.3, []_i = 16 mM, PCO₂ = 33 mm Hg. Point B represents the hypothetical case in which the reduction of pH_i resulting from removal is canceled by simultaneous reduction of PCO₂: pH_i = 7.3, []_i = 11 mM, PCO₂ = 23 mm Hg. Point C represents the actual conditions when is removed at unchanged PCO₂: pH_i = 7.2, []_i = 13 mM, PCO₂ = 33 mm Hg. The iso‐PCO₂ curves are constructed taking the “overall” pK₁′ of CO₂ as 6.1 and CO₂ solubility as 0.03 mmole 1⁻¹ mm Hg⁻¹. The slope of the parallel lines is a measure of the non‐ buffering power, which remains the same in the three conditions at an assumed value of 20 mM per pH unit. For details, see text.

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Robert W. Putnam, Albert Roos. Intracellular pH. Compr Physiol 2011, Supplement 31: Handbook of Physiology, Cell Physiology: 389-440. First published in print 1997. doi: 10.1002/cphy.cp140109

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