Key result
Decreasing intracellular pH to 5.8 inhibits Kir4.1 open-state probability by ~70% while increasing conductance.
Why the study?
The biophysical properties of Kir4.1 channels underlying the inhibition of whole-cell currents by decreased intracellular pH were not fully understood.
Intracellular protons exert opposite effects on the open-state probability and single channel conductance of Kir4.1 channels, which explains the changes in macroscopic currents observed at low pH.
Answers are grounded in this paper and cite their sources.
Acidosis effects on Kir4.1 may alter cardiac electrophysiology; extends channel biophysics but leaves clinical relevance open.
A decrease in intracellular pH (pHi) inhibits whole-cell Kir4.1 currents. To understand channel biophysical properties underlying this inhibition, single channel Kir4.1 currents were studied in inside-out patches using symmetric concentrations of K+ applied to each side of the plasma membrane. Under such conditions, inward rectifying currents were observed in about 2 of 3 patches. At pH 7.4, these currents showed a single channel conductance of 22 pS with a channel open-state probability (Popen) of approximately 0.9. 2. The effects of intracellular protons on macroscopic Kir4.1 currents were examined in giant inside-out patches at various pH levels of internal solutions. Current amplitude increased with a modest acidification (pH 7.0 and 6.6), and decreased with further reductions in pHi. The Kir4.1 currents were completely suppressed at pH 5.4. These effects were fast and reversible. 3. Low pHi inhibited Popen and enhanced single channel conductance in a concentration-dependent manner with pK (midpoint pH value for channel inhibition) of 6.0 and 6.8, respectively. At pH 5.8, Popen was inhibited by 70 % and single channel conductance increased by 35 %. Washout brought both Popen and single channel conductance rapidly back to baseline levels. 4. Theoretical currents were calculated using percentage changes in Popen and single channel conductance at each pH level tested. The trajectory of these currents is very close to that of experimental currents recorded from giant patches. Thus, opposite effects of intracellular protons on Popen and single channel conductance are demonstrated, which are likely to result in changes of macroscopic Kir4.1 currents with low pH.
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Yang et al. (1999) studied this question. Intracellular pH reduction vs. Baseline pH 7.4 was evaluated on Channel open-state probability (Popen) and single channel conductance. Decreasing intracellular pH to 5.8 inhibited the open-state probability of Kir4.1 channels by 70% while increasing single channel conductance by 35%.
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