Mechanisms of action of diltiazem in isolated human atrial and ventricular myocardium.

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Sutton MS, Morad M

Mechanisms of action of diltiazem in isolated human atrial and ventricular myocardium.

J Mol Cell Cardiol. 1987 May;19(5):497-508.

PubMed ID
3498047 [ View in PubMed
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Abstract

A comparative study of human atrial fibers (HAF), human ventricular fibers (HVF), frog ventricle, and frog skeletal muscle demonstrated marked differences in tension development in the presence of diltiazem. There was no significant difference between the tension developed by HAF and by HVF over a range of diltiazem concentrations when the differences in resting membrane potential were corrected by increasing external K+ concentration. In human myocardium, diltiazem resulted in both a voltage and use-dependent blockade of the calcium channel. Comparison of the tension-dose response curves in human myocardium, frog ventricle and skeletal muscle showed that diltiazem was most effective at decreasing tension in frog heart, and least effective in skeletal muscle with human myocardium being intermediate. In skeletal muscle, neither tension development nor the birefringence signal related to the Ca2+ release from the sarcoplasmic reticulum was significantly altered by Diltiazem in concentrations less than 10(-6) M, but in concentrations greater than 10(-5) M both were suppressed. Diltiazem suppressed tension in human myocardium over the range of membrane potentials associated with Ca2+ channel activity, while at more positive potentials, diltiazem appeared to have little effect on the tension-voltage relations. Diltiazem had no effect upon tension development induced by acetyl strophanthidin in human myocardium or upon the Ca2+ sensitivity of chemically skinned atrial or ventricular fibers. Thus the tension-suppressant effect of diltiazem in human myocardium appears to be mediated by a combination of voltage-dependent block of the Ca2+ channel and inhibition of Ca2+ release from internal stores, and not from alterations in either Na+-Ca2+ coupled transport or Ca2+ sensitivity of the myofilaments.

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