Histamine Activates the Chloride Current in Cardiac Ventricular Myocytes

Histamine Activation of ICl. Exposure of enzymatically dispersed guinea pig ventricular myocytes to histamine evoked a time‐independent background current that was measured using the whole cell patch‐clamp technique. This current was observed when Na+ currents were inactivated by membrane potential, and Ca2+ and K+ currents were blocked by channel antagonists and impermeant ions. Alterations of the CI− gradient caused a shift of the reversal potential of the histamine‐induced current expected for a CI− current. The histamine‐induced CI− current was attenuated by concurrent exposure of cells to acetylcholine, the H2 receptor antagonist cimetidine, and adenosine. In current‐clamp experiments, histamine‐induced changes in the action potential and resting membrane potential were dependent upon the CI− gradient across the membrane. The characteristics of the histamine‐induced CI− current resemble those of the CI− current, ICl elicited by isoproterenol, forskolin, adenosine 3′,5′‐cyclic monophosphate (cAMP), and cAMP‐dependent protein kinase in this preparation. It is concluded that histamine activates a similar CI− conductance in guinea pig ventricular myocytes through a cAMP‐dependent pathway. (J Cardiovasc Electrophysiol, Vol 1, pp. 309–317, 1990)