Figure 4.

Targeted disruption of eNOS does not affect muscarinic activation of acetylcholine-sensitive K⁺ current (I_K(ACh)). (A) The activation of I_K(ACh) in an eNOS^null atrial myocyte is illustrated at a holding potential of −40 mV and after a ramp pulse from −150 to +60 mV, applied to the cell at 0.1V/s. I_Ca-L was blocked by 0.4 mM Cd²⁺. The fast inward sodium current also was blocked largely by Cd²⁺. (B) A comparison of I_K(ACh) from eNOS^null (n = 5) and WT (n = 7) atrial myocytes. The amplitude of I_K(ACh) was determined as the difference current level at −100 mV. (C) The activation of I_K(ACh) in an eNOS^null ventricular myocyte. A hyperpolarization pulse from a holding potential of −40 mV to −100 mV was applied to the cell, and traces a, b, and c were recorded under control conditions, with CCh (1 μM) application, and after washout of CCh, respectively. (D) The current–voltage relationship of I_K(ACh) in an eNOS^null ventricular myocyte. The ramp pulse was identical to that described in A. I_Ca-L and sodium current were blocked by Cd²⁺ (0.4 mM). Traces a, b, and c were recorded under control conditions, with CCh (1 μM), and with atropine (1 μM) in the continuous presence of CCh. (E) A comparison of I_K(ACh) (at −100 mV) from both eNOS^null (n = 8) and WT (n = 7) ventricular myocytes. (F) Activation of I_K(ACh) in an eNOS^null ventricular myocyte abbreviates action potential duration. Traces a, b, and c were recorded under control conditions (a), during CCh (1 μM) application (b), and with atropine (1 μM) in the continuous presence of CCh (c).