Inhibition of High K + and Norepinephrine-Induced Free Intracellular Calcium by Tetrandrine in Dissociated Rabbit Retina Cells

Abstract

ABSTRACT

The effects of tetrandrine (Tet) on the changes of intracellular free Ca²⁺ concentration ([Ca²⁺]i) induced by high concentration of K⁺ and norepinephrine in 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 μM did not affect the resting [Ca²⁺]i when the extracellular Ca²⁺ concentration was in the range of 0-2 mM. Tet at 1-100 μM suppressed the [Ca²⁺]i elevation induced by a high concentration of K+ in a concentration-dependent manner, when the concentration of K⁺ was 50 mM IC₅₀ for Tet was 10.9 μM. Although Tet at high concentration (30 μM) suppressed the [Ca²⁺]i increases induced by norepinephrine (0.1-100 nM) in the presence of Ca²⁺ at 1.3 mM, it failed to do the same at lower concentration of Tet (1-10 μM), however, Tet at 30 μM did not effect the release of intracellular Ca²⁺ stored in the sarcoplasmic reticulum in the Ca2+-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-opereted ionic channels in retina cells.