1988
DOI: 10.1085/jgp.91.5.641
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Hydrogen ion modulation of Ca channel current in cardiac ventricular cells. Evidence for multiple mechanisms.

Abstract: We have investigated the effects of H ions on (L-type) Ca channel current in isolated ventricular cells. We find that the current amplitude is enhanced in solutions that are alkaline relative to pH 7.4 and reduced in solutions acidic to this pH. We measured pHo-induced shifts in channel gating and analyzed our results in terms of surface potential theory. The shifts are well described by changes in surface potential caused by the binding of H ions to negative charges on the cell surface. The theory predicts a … Show more

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Cited by 93 publications
(89 citation statements)
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References 44 publications
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“…Taken together, acidosis will influence Ito differently in different regions of the heart according to the actual resting membrane potential, an action which can alter action potential dispersion and contribute to arrhythmogenesis under ischaemic conditions. Similar shifts of the voltage dependence of Na¤ and Ca¥ channel gating induced either by extracellular protons or by divalent cations have been described in a variety of tissues (Schauf, 1975;Ohmori & Yoshii, 1977;Kostyuk et al 1982;Krafte & Kass, 1988;Zhang & Siegelbaum, 1991;Huang et al 1993;Davidson et al 1995). The phenomenon is usually explained by the surface charge theory, according to which the titration of negative external surface charges leads to changes in surface potential and therefore to changes in the potential sensed by the voltage sensor of the channel.…”
Section: Discussionmentioning
confidence: 61%
See 1 more Smart Citation
“…Taken together, acidosis will influence Ito differently in different regions of the heart according to the actual resting membrane potential, an action which can alter action potential dispersion and contribute to arrhythmogenesis under ischaemic conditions. Similar shifts of the voltage dependence of Na¤ and Ca¥ channel gating induced either by extracellular protons or by divalent cations have been described in a variety of tissues (Schauf, 1975;Ohmori & Yoshii, 1977;Kostyuk et al 1982;Krafte & Kass, 1988;Zhang & Siegelbaum, 1991;Huang et al 1993;Davidson et al 1995). The phenomenon is usually explained by the surface charge theory, according to which the titration of negative external surface charges leads to changes in surface potential and therefore to changes in the potential sensed by the voltage sensor of the channel.…”
Section: Discussionmentioning
confidence: 61%
“…Ito plays an important role in the early repolarization phase of the cardiac action potential and its variable regional density underlies the heterogeneity of the action potential within the ventricular wall (Antzelevitch et al 1991). Extracellular acidosis is known to influence many membrane currents (see Krafte & Kass, 1988;Zhang & Siegelbaum, 1991). Protons and divalent cations induce a shift of voltagedependent channel gating which is usually explained by a screening of membrane surface charge which changes the potential sensed by the voltage sensor of the channels (see Hille, 1984).…”
mentioning
confidence: 99%
“…The reduction in I Ca results from both an inhibition of the peak amplitude of I Ca and a positive shift in I Ca activation. The former effect results from proton block of the channel, the latter results from neutralization of membrane surface charge (Krafte and Kass, 1988;Barnes and Bui, 1991;Klockner and Isenberg, 1994). Thus, the release of protons that accompanies release of L-glutamate acts as a negative feedback mechanism to inhibit I Ca and reduce further exocytosis.…”
Section: Vesicular Zinc-znmentioning
confidence: 99%
“…Such high concentrations of divalent cations screen negative surface charges much more effectively than would physiological concentrations of Ca 2ϩ (Frankenhaeuser and Hodgkin, 1957;Krafte and Kass, 1988;Green and Andersen, 1991), resulting in potentially large, but as-yet-undetermined depolarizing voltage shifts in the gating properties observed at the single-channel level. The unspecified magnitude of this voltage shift constituted a particularly critical ambiguity in this study, because earlier macroscopic current experiments (using physiological Ca 2ϩ ) indirectly hinted that the prevalence of reluctant openings may increase sharply with depolarization (Colecraft et al, 2000).…”
Section: Large Surface-potential Shifts Complicate Physiological Intementioning
confidence: 99%