Journal
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
Volume 21, Issue 10, Pages 1160-1169Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1540-8167.2010.01772.x
Keywords
acidosis; arrhythmia; action potential; hERG; potassium channel
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Funding
- Heart Research UK [RG2541]
- University of Bristol
- UK ORSAS award
- British Heart Foundation
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Methods and Results: I(hERG) recordings were made from hERG-expressing Chinese Hamster Ovary cells using whole-cell patch-clamp at 37 degrees C. I(hERG) during action potential (AP) waveforms was rapidly suppressed by reducing external pH from 7.4 to 6.3. Peak repolarizing current and steady state I(hERG) activation were shifted by similar to+6 mV; maximal I(hERG) conductance was reduced. The voltage-dependence of I(hERG) inactivation was little-altered. Fast and slow time-constants of I(hERG) deactivation were smaller across a range of voltages at pH 6.3 than at pH 7.4, and the contribution of fast deactivation increased. A modest acceleration of the time-course of recovery of I(hERG) from inactivation was observed, but time-course of activation was unaffected. The amplitude of outward I(hERG) transients elicited by premature stimuli following an AP command was significantly decreased at lower pH. Computer simulations showed that after AP repolarization a subthreshold stimulus at pH 7.4 could evoke an AP at pH 6.3. Conclusion: During acidosis the contribution of I(hERG) to action potential repolarization is reduced and hERG may be less effective in counteracting proarrhythmogenic depolarizing stimuli. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1160-1169).
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