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Influence of Cardiac Dysfunction on Fast Sodium Current Regulation by Forskolin
Author(s) -
KIRSTEIN MICHAEL,
KATZER ASTRID,
HU KAI,
GAUDRON PETER,
ERTL GEORG,
LANGENFELD HEINER,
KOCHSIEK KURT
Publication year - 1996
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/j.1540-8159.1996.tb03273.x
Subject(s) - medicine , forskolin , current (fluid) , sodium , sodium channel , cardiology , electrical engineering , metallurgy , stimulation , materials science , engineering
There are several reports of an altered β‐adrenergic pathway in heart failure. Since the fast cardiac sodium current (I NA+ ) is also subject to β‐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 β‐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, I Na+ 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 mmRgj, forskolin (3 mmol/L) increased the maximal available I Na + 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 induced increase of I NA + in rats with significant myocardial infarctions, this increase remalns the same when adenylyl cyclase is stimulated directly. This is consistent with a direct β‐receptor down‐regulation or desensitization.