Guanine Nucleotide-, and Inositol Triphosphate-induced Inhibition of the CA2+ Pump in Rat Heart Sarcolemmal Vesicles

The Ca2+ pump of rat heart sarcolemma has been studied via its ATP-dependent Ca2+ transport and (Ca2+ + Mg2+)-dependent ATPase activities. Direct incubation of the sarcolemmal vesicles with micromolar concentration of guanosine 5'-O-(thiotriphosphate) (GTP gamma S) results in the reduction of Ca2+ uptake by 34 +/- 10% and ATP hydrolysis by 55 +/- 7%. Similar inhibition of the sarcolemmal Ca2+ pump is also observed with micromolar concentration of inositol trisphosphate (IP3), while GDP or inositol tetrakisphosphate (IP4) has no effect. Based on the evidence that these sarcolemmal vesicles are capable of generating IP3 upon stimulation by GTP gamma S, and that no additive effect is observed when both agents are incubated together with the membranes, it is concluded that the effect of GTP gamma S on the Ca2+ pump is mediated by IP3. The results here show for the first time that plasma membrane Ca2+ pump has a role in the primary Ca2+ signaling.