Regulation of the cAMP-Dependent Chloride Current in Cardiac Ventricular Myocytes
The contribution, if any, of Cl− to the electrical activity in cardiac muscle has been debated since the first reports that altering the extracellular Cl− concentration caused changes in the shape of the action potential and rate of spontaneous depolarization in Purkinje fibers (Nutter and Noble, 1961; Carmeliet, 1961). However, it was not until recently that conclusive evidence for a cardiac Cl− conductance was found in ventricular myocytes (Harvey and Hume, 1989a; Bahinski et al., 1989). One reason it took so long to discover this Cl− current may be explained by the unusual way it is regulated. In isolated myocytes, the Cl− current does not appear to be activated unless intracellular cAMP is elevated above basal levels (Harvey and Hume, 1989a; Bahinski et al., 1989), which is a unique feature among ion channels in cardiac tissue. Another unusual characteristic of this Cl− current is the fact it exhibits an unexpected dependence on Na+ Early observations found that replacement of extracellular Na+ attenuated the Cl− current activated by ß-adrenergic stimulation without affecting its reversal potential (Bahinski et al, 1989; Harvey et al., 1990), suggesting that the ß-adrenergic induced current was Na+-sensitive, but not conducted by Na+ The purpose of the present report is to describe work that has been carried out to identify mechanisms involved in the regulation of the cAMP-dependent Cl− current found in cardiac myocytes.
KeywordsLithium Attenuation Adenosine Histamine Epinephrine
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