CA2-INDUCED INHIBITION OF CA-45(2+) INFLUX AND CA2+ CURRENT IN SMOOTH-MUSCLE OF THE RAT VAS-DEFERENS()

The present study investigates how changes in intracellular Ca2+ conce ntration modulate the influx of Ca-45(2+) in isolated rat vasa deferen tia. Raising extracellular K+ concentration ([K+](o)) to greater than or equal to 32 mM increased Ca-45(2+) influx during the Ist min in sol utions containing 0.03-1.5 mM extracellular Ca2+ concentration ([Ca2+] (o)). During the 6th min in [K+](o) greater than or equal to 50 mM, Ca -45(2+) influx was less than during the 1st min. This decline in Ca-45 (2+) influx occurred for [Ca2+](o) greater than or equal to 0.4 mM. Pr ocaine potentiated K+-stimulated Ca-45(2+) influx in 1.5 mM [Ca2+](o) and eliminated the decline of Ca-45(2+) influx in low [Ca2+](o). Ryano dine and norepinephrine reduced K+-stimulated Ca-45(2+) influx. Ca-45( 2+) content changed with time in accordance with the changes observed in Ca-45(2+) influx. In isolated cells, voltage-dependent inward curre nts inactivated more rapidly with 1.5 mM Ca2+ as the charge carrier th an with 1.5 mM Ba2+, and the steady-state inactivation relationship wa s shifted in the hyperpolarizing direction. Inward current was reduced with either caffeine, ryanodine, or norepinephrine. The inhibitory ef fects of norepinephrine were abolished by depletion of intracellular C a2+ stores. These results are compatible with the hypothesis that K+-s timulated Ca-45(2+) influx declines with time due to Ca2+-induced inhi bition of Ca2+ channels. Ca2+- and inositol 1,4,5-trisphosphate-induce d releases of Ca2+ from the sarcoplasmic reticulum appear to play an i mportant role in this process.