Alkali cation permeability and caesium blockade of cromakalim‐activated current in guinea‐pig ventricular myocytes

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Abstract
1 The sensitivity of cromakalim-activated current (Icrom) to manipulations of extracellular cationic composition was examined in whole-cell voltage clamp recordings from freshly-dispersed, adult guinea-pig ventricular myocytes. In bathing media with different concentrations of K+ (1, 2.5, 5.4 and 12 mm) the Icrom reversal potential (Erev) varied in strict correspondance with the K+ equilibrium potential and inward Icrom amplitude was proportional to the external K+ concentration. 2 Replacement of 12 mm K+ with 12 mm Rb+ induced a slight positive shift of Erev indicating that PRb+/PK+ = 1.06. K+ replacement with 12 mm Cs+ reduced or abolished inward Icrom and produced a negative shift of Erev by at least 50 mV; an upper limit of PCs+/PK+ was fixed at 0.18. 3 Addition of Rb+ (1–30 mm) to 2.5 mm K+-containing medium produced a concentration-dependent increase in inward Icrom and positive shift of Erev suggesting that K+ and Rb+ have similar permeabilities and conductivities and do not interfere with each other in the channel. 4 Cs+ (0.01–30 mm), added to medium containing 12 mm Rb+, induced a potent, voltage-dependent inhibition of inwardly rectifying current (IK1; IC50 = 0.2–3 mm). Voltage-dependent inhibition of inward Icrom was observed only at considerably higher Cs+ concentrations (IC50 = 4–30 mm). Extracellular Rb+ and Cs+ did not substantially alter the amplitude of outward Icrom. 5 The results support the contention that the ATP-sensitive K+ channel is the primary target of cromakalim action in ventricular myocytes.