Regulation of InsP3-induced contractions by myoplasmic calcium in permeabilized atrial muscle.
OBJECTIVE
We studied the effect of calcium on inositol 1,4,5-trisphosphate (InsP3)-induced contractions in saponin-permeabilized chick atrial muscle (80-100 microns in diameter). Calcium has been proposed to modulate InsP3-induced response and InsP3 binding in other tissue.


METHODS
A transient increase in tension was used to detect the release of calcium in this multicellular preparation. Pulsed (2-3 s) superfusion of either calcium or InsP3 produced a transient contraction.


RESULTS
Pulsed coapplication of both InsP3 and calcium resulted in a contraction greater than that predicted by an additive effect of both intracellular messengers. The release of calcium by InsP3 is positively and negatively modulated by myoplasmic calcium (EC50 congruent to 0.17 microM and IC50 of approximately 1.5 microM). The peak potentiation occurred at approximately pCa = 6.3 (0.51 microM free calcium).


CONCLUSIONS
These observations indicate that an increase of InsP3 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 release during excitation-contraction (E-C) coupling, we propose that changes in cytoplasmic calcium can modulate InsP3-induced calcium release on a beat-to-beat basis. Thus, InsP3 may regulate force generation during E-C coupling by activating calcium release during a heart beat.
Vites
A M
AM
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA.
Pappano
A J
AJ
D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D004347:Drug Interactions; D004594:Electrophysiology; D006325:Heart Atria; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D013268:Stimulation, Chemical
D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium