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Proton Modulation of Cardiac I Na: A Potential Arrhythmogenic Trigger

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Voltage Gated Sodium Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 221))

Abstract

Voltage-gated sodium (NaV) channels generate the upstroke and mediate duration of the ventricular action potential, thus they play a critical role in mediating cardiac excitability. Cardiac ischemia triggers extracellular pH to drop as low as pH 6.0, within just 10 min of its onset. Heightened proton concentrations reduce sodium conductance and alter the gating parameters of the cardiac-specific voltage-gated sodium channel, NaV1.5. Most notably, acidosis destabilizes fast inactivation, which plays a critical role in regulating action potential duration. The changes in NaV1.5 channel gating contribute to cardiac dysfunction during ischemia that can cause syncope, cardiac arrhythmia, and even sudden cardiac death. Understanding NaV channel modulation by protons is paramount to treatment and prevention of the deleterious effects of cardiac ischemia and other triggers of cardiac acidosis.

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  1. University of Wisconsin-Madison, Madison, WI, USA

    David K. Jones

  2. Simon Fraser University, Burnaby, BC, Canada

    Peter C. Ruben

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  1. David K. Jones
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Correspondence to David K. Jones .

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  1. Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada

    Peter C. Ruben

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Jones, D.K., Ruben, P.C. (2014). Proton Modulation of Cardiac I Na: A Potential Arrhythmogenic Trigger. In: Ruben, P. (eds) Voltage Gated Sodium Channels. Handbook of Experimental Pharmacology, vol 221. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41588-3_8

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