The goal of the research in this proposal is to learn more about the chloride (Cl) current recently discovered in cardiac myocytes. Very little is known about this current except that it can be elicited following beta- adrenergic stimulation, and it appears to play an important role in regulating action potential duration. The proposed experiments will (i) characterize the biophysical properties of this current at the whole cell and single channel level, (ii) investigate the mechanisms through which agonists and ions regulate the activity of this current, (iii) determine the effect of pharmacologic agents known to block Cl channels in other preparations, and (iv) define the physiological role of the Cl current in controlling electrical activity in the heart. This information will provide a better understanding of the physiological regulation of cardiac function and may provide insight into future approaches to the treatment of arrhythmias.
| Harvey, R D (1993) Effects of stilbenedisulfonic acid derivatives on the cAMP-regulated chloride current in cardiac myocytes. Pflugers Arch 422:436-42 |
| Overholt, J L; Hobert, M E; Harvey, R D (1993) On the mechanism of rectification of the isoproterenol-activated chloride current in guinea-pig ventricular myocytes. J Gen Physiol 102:871-95 |
| Zakharov, S I; Overholt, J L; Wagner, R A et al. (1993) Tetramethylammonium activation of muscarinic receptors in cardiac ventricular myocytes. Am J Physiol 264:C1625-30 |
| Harvey, R D; Jurevicius, J A; Hume, J R (1991) Intracellular Na+ modulates the cAMP-dependent regulation of ion channels in the heart. Proc Natl Acad Sci U S A 88:6946-50 |
| Hume, J R; Harvey, R D (1991) Chloride conductance pathways in heart. Am J Physiol 261:C399-412 |
