Inhibition of high K+ and norepinephrine-induced free intracellular calcium by tetrandrine in dissociated rabbit retina cells.

Abstract

The effect of tetrandrine (Tet) on the changes of intracellular free Ca2+ concentration ([Ca2+]i) induced by high concentration of K+ and norepinephrine is dissociated rabbit retina cells were studied. The changes of [Ca2+]i were reflected by the fluorescent indicator, Fura-2/AM, employed. The resting [Ca2+]i was 223 +/- 27 nM in Hank's solution containing 1.3 mM Ca2+. Tet at 30 microM did not affect the resting [Ca2+]i when the extracellular Ca2+ concentration was in the range of 0-2 mM. Tet at 1-100 microM suppressed the [Ca2+]i elevation induced by high concentration of K+ in a concentration-dependent manner. When the concentration of K+ was 50 mM IC50 for Tet was 10.9 microM. Although Tet at high concentration (30 microM) suppressed the [Ca2+]i increases induced by norepinephrine (0.1-100 nM) in the presence of Ca2+ at 1.3 mM, failed to do the same at lower concentration of Tet (1-10 microM), however, Tet at 30 microM did not effect the release of intracellular Ca2+ stored in the sarcoplasmic reticulum in the Ca(2+)-free Hank's solution. These results indicate that Tet is able to block Ca2+ influx from extracellular site via voltage-sensitive ionic channels and at high concentration via receptor-operated ionic channels in retina cells.