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.
KeywordsCardiac Myocytes Ventricular Myocytes Purkinje Fiber Chloride Current Intracellular Solution
Unable to display preview. Download preview PDF.
- Harvey RD, Clark CD, Hume JR (1990) Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential. J Gen Physiol 95: 1077–1102.Google Scholar
- Harvey RD, Jurevicius JA, Hume JR (1991) Intracellular Na+ modulates the cAMPdependent regulation of ion channels in the heart. Proc Natl Acad Sci USA in press.Google Scholar
- Huffer OF, Noble D (1961) Anion conductance of cardiac muscle. J Physiol 157: 335–350.Google Scholar
- Hwang T, Hone M, Gadsby D (1991) Persistent activation of chloride current by GTP-y-S in guinea pig ventricular myocytes. Biophys J 59: 7a.Google Scholar