Figure 2.

Modulation of cardiac electrical activity by activation of Cl⁻ channels in heart. Changes in action potentials (top), membrane currents (middle), and ECG (bottom) due to activation of CFTR or volume-regulated ClC-3 Cl⁻ channels are depicted. Top panel: 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. Middle panel: range of zero-current values corresponding to E_Cl is shown in grey. Activation of CFTR or ClC-3 channels generates both inward (indicated by green) and outward (indicated by red) currents and cause both depolarization as well as repolarization during the action potential. Activation of I_Cl, therefore, induces larger membrane depolarization and induction of early afterdepolarizations under conditions where resting K⁺ conductance is reduced (dotted red lines in top panel). Bottom panel: the letters (P, Q, R, S, and T) indicate the conventional waves of electrocardiograph (ECG) complex under control conditions (black) and after activation of I_Cl (red). Corresponding to the shortening of action potential in ventricular myocytes activation of I_Cl causes a shortening of Q–T interval. See text for details (48). (Copyright Request: Duan D. J Physiol 587: 2163–2177, 2009.)