Ca(2+)-induced inhibition of 45Ca2+ influx and Ca2+ current in smooth muscle of the rat vas deferens.

The present study investigates how changes in intracellular Ca 2+ concentration modulate the influx of 45 Ca 2+ in isolated rat vasa deferentia. Raising extracellular K + concentration ([K + ] o ) to ≥32 mM increased 45 Ca 2+ influx during the 1st min in solutions containing 0.03-1.5 mM extracellular Ca 2+ concentration ([Ca 2+ ] o ) During the 6th min in [K + ] o ≥50 mM, 45 Ca 2+ influx was less than during the 1st min. This decline in 45 Ca 2+ influx occurred for [Ca 2+ ] o ≥0.4 mM. Procaine potentiated K + -stimulated 45 Ca 2+ influx in 1.5 mM [Ca 2+ ] o and eliminated the decline of 45 Ca 2+ influx in low [Ca 2+ ] o . Ryanodine and norepinephrine reduced K + -stimulated 45 Ca 2+ influx. 45 Ca 2+ content changed with time in accordance with the changes observed in 45 Ca 2+ influx. In isolated cells, voltage-dependent inward currents inactivated more rapidly with 1.5 mM Ca 2+ as the charge carrier than with 1.5 mM Ba 2+ , and the steady-state inactivation relationship was shifted in the hyperpolarizing direction. Inward current was reduced with either caffeine, ryanodine, or norepinephrine. The inhibitory effects of norepinephrine were abolished by depletion of intracellular Ca 2+ stores. These results are compatible with the hypothesis that K + -stimulated 45 Ca 2+ influx declines with time due to Ca 2+ -induced inhibition of Ca 2+ channels. Ca 2+ - and inositol 1,4,5-trisphosphate-induced releases of Ca 2+ from the sarcoplasmic reticulum appear to play an important role in this process.