Interactions between H+ and Ca2+ near cardiac L-type calcium channels: evidence for independent channel-associated binding sites

Kwan, Yiu Wa; Kass, Robert S.

doi:10.1016/s0006-3495(93)81152-4

Cited by 20 publications

(23 citation statements)

References 44 publications

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“…Decreases in calcium current with acidification may be caused by 1) block of the permeation pathway; 2) decrease in local calcium concentrations, and; 3) proton modification of gating. An increase of external proton concentration shifts the voltage dependence of HVA calcium channels gating to more depolarized potentials (e.g., Krafte and Kass, 1988;Kwan and Kass, 1993). This shift effect is similar to that noted for voltage-gated sodium channels (Woodhull, 1973), and T-type calcium channels in cardiac myocytes (Tytgat et al, 1990).…”

Section: Introductionsupporting

confidence: 64%

pH Modification of Human T-Type Calcium Channel Gating

Delisle

Satin

2000

Biophysical Journal

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External pH (pH(o)) modifies T-type calcium channel gating and permeation properties. The mechanisms of T-type channel modulation by pH remain unclear because native currents are small and are contaminated with L-type calcium currents. Heterologous expression of the human cloned T-type channel, alpha1H, enables us to determine the effect of changing pH on isolated T-type calcium currents. External acidification from pH(o) 8.2 to pH(o) 5.5 shifts the midpoint potential (V(1/2)) for steady-state inactivation by 11 mV, shifts the V(1/2) for maximal activation by 40 mV, and reduces the voltage dependence of channel activation. The alpha1H reversal potential (E(rev)) shifts from +49 mV at pH(o) 8.2 to +36 mV at pH(o) 5.5. The maximal macroscopic conductance (G(max)) of alpha1H increases at pH(o) 5.5 compared to pH(o) 8.2. The E(rev) and G(max) data taken together suggest that external protons decrease calcium/monovalent ion relative permeability. In response to a sustained depolarization alpha1H currents inactivate with a single exponential function. The macroscopic inactivation time constant is a steep function of voltage for potentials < -30 mV at pH(o) 8.2. At pH(o) 5.5 the voltage dependence of tau(inact) shifts more depolarized, and is also a more gradual function of voltage. The macroscopic deactivation time constant (tau(deact)) is a function of voltage at the potentials tested. At pH(o) 5.5 the voltage dependence of tau(deact) is simply transposed by approximately 40 mV, without a concomitant change in the voltage dependence. Similarly, the delay in recovery from inactivation at V(rec) of -80 mV in pH(o) 5.5 is similar to that with a V(rec) of -120 mV at pH(o) 8.2. We conclude that alpha1H is uniquely modified by pH(o) compared to other calcium channels. Protons do not block alpha1H current. Rather, a proton-induced change in activation gating accounts for most of the change in current magnitude with acidification.

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Section: Introductionsupporting

confidence: 64%

pH Modification of Human T-Type Calcium Channel Gating

Delisle

Satin

2000

Biophysical Journal

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“…Conversely, acidification increases positive charge on the membrane surface and elevates I Ca threshold, shifting the voltage-dependence of activation to more positive values. Effects of protons on surface charge can be observed even in the presence of divalent cations suggesting that protons and divalent cations act at partially independent binding sites (Kwan and Kass, 1993). …”

Section: Negative Feedback From Horizontal Cells To Conesmentioning

confidence: 99%

Lateral interactions in the outer retina

Thoreson

Mangel

2012

Progress in Retinal and Eye Research

228

225

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Lateral interactions in the outer retina, particularly negative feedback from horizontal cells to cones and direct feed-forward input from horizontal cells to bipolar cells, play a number of important roles in early visual processing, such as generating center-surround receptive fields that enhance spatial discrimination. These circuits may also contribute to post-receptoral light adaptation and the generation of color opponency. In this review, we examine the contributions of horizontal cell feedback and feed-forward pathways to early visual processing. We begin by reviewing the properties of bipolar cell receptive fields, especially with respect to modulation of the bipolar receptive field surround by the ambient light level and to the contribution of horizontal cells to the surround. We then review evidence for and against three proposed mechanisms for negative feedback from horizontal cells to cones: 1) GABA release by horizontal cells, 2) ephaptic modulation of the cone pedicle membrane potential generated by currents flowing through hemigap junctions in horizontal cell dendrites, and 3) modulation of cone calcium currents (ICa) by changes in synaptic cleft proton levels. We also consider evidence for the presence of direct horizontal cell feed-forward input to bipolar cells and discuss a possible role for GABA at this synapse. We summarize proposed functions of horizontal cell feedback and feed-forward pathways. Finally, we examine the mechanisms and functions of two other forms of lateral interaction in the outer retina: negative feedback from horizontal cells to rods and positive feedback from horizontal cells to cones.

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“…An additional problem in some work is likely to have been inadequate inhibition of NHE activity (Kohlhardt et al, 1976;Yatani and Goto, 1983;Krafte and Kass, 1988;Kwan and Kass, 1993;F. Chen et al, 1996; using the AP-clamp technique) produced only small effects on net Ca 2+ entry.…”

Section: Comparison With Previous Workmentioning

confidence: 99%

Influence of pH on Ca2+ current and its control of electrical and Ca2+ signaling in ventricular myocytes

Saegusa

Moorhouse

Vaughan‐Jones

et al. 2011

Journal of General Physiology

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Modulation of L-type Ca2+ current (ICa,L) by H+ ions in cardiac myocytes is controversial, with widely discrepant responses reported. The pH sensitivity of ICa,L was investigated (whole cell voltage clamp) while measuring intracellular Ca2+ (Ca2+i) or pHi (epifluorescence microscopy) in rabbit and guinea pig ventricular myocytes. Selectively reducing extracellular or intracellular pH (pHo 6.5 and pHi 6.7) had opposite effects on ICa,L gating, shifting the steady-state activation and inactivation curves to the right and left, respectively, along the voltage axis. At low pHo, this decreased ICa,L, whereas at low pHi, it increased ICa,L at clamp potentials negative to 0 mV, although the current decreased at more positive potentials. When Ca2+i was buffered with BAPTA, the stimulatory effect of low pHi was even more marked, with essentially no inhibition. We conclude that extracellular H+ ions inhibit whereas intracellular H+ ions can stimulate ICa,L. Low pHi and pHo effects on ICa,L were additive, tending to cancel when appropriately combined. They persisted after inhibition of calmodulin kinase II (with KN-93). Effects are consistent with H+ ion screening of fixed negative charge at the sarcolemma, with additional channel block by H+o and Ca2+i. Action potential duration (APD) was also strongly H+ sensitive, being shortened by low pHo, but lengthened by low pHi, caused mainly by H+-induced changes in late Ca2+ entry through the L-type Ca2+ channel. Kinetic analyses of pH-sensitive channel gating, when combined with whole cell modeling, successfully predicted the APD changes, plus many of the accompanying changes in Ca2+ signaling. We conclude that the pHi-versus-pHo control of ICa,L will exert a major influence on electrical and Ca2+-dependent signaling during acid–base disturbances in the heart.

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Interactions between H+ and Ca2+ near cardiac L-type calcium channels: evidence for independent channel-associated binding sites

Cited by 20 publications

References 44 publications

pH Modification of Human T-Type Calcium Channel Gating

pH Modification of Human T-Type Calcium Channel Gating

Lateral interactions in the outer retina

Influence of pH on Ca2+ current and its control of electrical and Ca2+ signaling in ventricular myocytes

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