Figure 11.

Modulation of cardiac electrical activity by activation of ClC-2 channels in cardiac pacemaker cells and myocytes. Changes in action potentials (top panels) and membrane currents (bottom panels) of cardiac pacemaker cells (A) or atrial and ventricular myocytes (B) due to activation of ClC-2 channels are depicted. I_Cl,ir is activated by hyperpolarization, cell swelling, and acidosis. Top panels: numbers illustrate conventional phases of a prototype ventricular action potential under control conditions (black) and after activation of I_Cl (red). Range of estimates for normal physiological values for Cl⁻ equilibrium potential (E_Cl) is indicated in blue. Bottom panels: range of zero-current values corresponding to E_Cl is shown in grey. (A) Activation of I_Cl,ir in pacemaker cells during hyperpolarization causes acceleration of phase 4 depolarization and automaticity, shortening of action potential duration, and decrease in cycle length and action potential amplitude (dashed red line in top panel). (B) Activation of I_Cl,ir in atrial and ventricular myocytes during hyperpolarization causes depolarization of resting membrane potential and induction of phase 4 auto depolarization and abnormal electrical impulse (trigger activity) and automaticity (dotted red line in top panel). [Adapted, with permission, from Duan (48)]. (Copyright Request: Duan D. J Physiol 587: 2163-2177, 2009)