REGULATION OF INSP(3)-INDUCED CONTRACTIONS BY MYOPLASMIC CALCIUM IN PERMEABILIZED ATRIAL MUSCLE

Objective: We studied the effect of calcium on inositol 1,4,5-trisphos phate (InsP(3))-induced contractions in saponin-permeabilized chick at rial muscle (80-100 mu m in diameter). Calcium has been proposed to mo dulate InsP(3)-induced response and InsP(3) binding in other tissue. M ethods: A transient increase in tension was used to detect the release of calcium in this multicellular preparation. Pulsed (2-3 s) superfus ion of either calcium or InsP(3) produced a transient contraction. Res ults: Pulsed coapplication of both InsP(3) and calcium resulted in a c ontraction greater than that predicted by an additive effect of both i ntracellular messengers. The release of calcium by InsP(3) is positive ly and negatively modulated by myoplasmic calcium (EC(50) similar or e qual to 0.17 mu M and IC50 of approximately 1.5 mu M) The peak potenti ation occurred at approximately pCa = 6.3 (0.51 mu M free calcium). Co nclusions: These observations indicate that an increase of InsP(3) in the heart, as produced by cardiac neurotransmitters and hormones, may regulate the force of contraction by virtue of its synergistic action with calcium. While calcium remains the primary trigger for calcium re lease during excitation-contraction (E-C) coupling, we propose that ch anges in cytoplasmic calcium can modulate InsP(3)-induced calcium rele ase on a beat-to-beat basis. Thus, InsP(3) may regulate force generati on during E-C coupling by activating calcium release during a heart be at.