PMID: 8945089Nov 1, 1996Paper

Influence of cardiac dysfunction on fast sodium current regulation by Forskolin

Pacing and Clinical Electrophysiology : PACE
Michael KirsteinK Kochsiek

Abstract

There are several reports of an altered beta-adrenergic pathway in heart failure. Since the fast cardiac sodium current (INa+) is also subject to beta-receptor dependent regulation, we investigated its regulation in a model of cardiac dysfunction. Adenylyl cyclase was stimulated directly with forskolin as one step in the beta-adrenergic pathway. Twelve-week-old Wistar rats were infarcted by ligation of the left anterior descending coronary artery. Eight weeks later, the induced hemodynamic changes were evaluated. The left ventricular end-diastolic pressure (LVEDP) was used as a measure of the hemodynamic effects of the myocardial infarction. With the loose patch clamp technique, INa+ was measured in intact papillary muscles at an external sodium concentration of 150 mmol/L. Potential dependent availability was tested with pulses to 0 mV from various conditioning potentials. In animals with minor infarction (n = 7, LVEDP = 7.7 +/- 0.9 mmHg), forskolin (3 mumol/L) increased the maximal available INa+ to 109% +/- 13% of baseline values. This increase was nearly the same in the group with significant infarctions (n = 7, LVEDP = 15.7 +/- 1.6 mmHg) to 113% +/- 6%. Thus, although we previously observed a reduction of the isoproterenol...Continue Reading

References

Jan 1, 1992·Circulation Research·J J MatsudaE F Shibata
Apr 1, 1990·The American Journal of Physiology·B SchubertA M Brown
Nov 1, 1990·Experimental Physiology·R BonvalletO Rougier
Aug 1, 1990·Circulation·M R Bristow
Jun 1, 1989·The American Journal of Physiology·K OnoM Arita
May 1, 1974·The Journal of General Physiology·C M Armstrong, F Bezanilla
Nov 1, 1994·Pacing and Clinical Electrophysiology : PACE·M KirsteinK Kochsiek
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·J Jurevicius, R Fischmeister

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