Inositol 1,4,5-trisphosphate releases intracellular Ca2+ in permeabilized chick atria.
Inositol 1,4,5-trisphosphate (IP3) and caffeine evoked transient, reversible, and concentration-dependent increases in tension in saponin-treated chick atrial muscle. Contractures evoked by IP3 and caffeine were detected in solutions with 70 microM EGTA at pCa 7.0. In the presence of 7 mM EGTA, neither IP3 nor caffeine was able to evoke a contracture. Maximally effective concentrations of IP3 (20 microM) and caffeine (20 mM) developed tensions to approximately 44 and 83% of that elicited by pCa 5.0 (maximum tension = 100%), respectively. The IP3- or caffeine-induced contractures were consistently reproduced when the sarcoplasmic reticulum (SR) had previously been loaded with calcium. Preexposure to caffeine suppressed the following IP3-induced response. When ryanodine (1-10 microM) was present throughout the SR-loading cycle, the responses to IP3 and caffeine were prevented. However, when ryanodine was added after the SR was loaded with calcium, neither the response to IP3 nor that to caffeine was affected. These results are consistent with the hypothesis that ryanodine inhibition requires prior activation of the SR calcium-release channel. It is concluded that both IP3 and caffeine increased tension in the SR by releasing calcium from it. The effect of IP3 is consistent with its messenger role as a calcium-mobilizing agent.
Vites
A M
AM
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
Pappano
A
A
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002645:Chickens; D005110:Extracellular Space / Q000378:metabolism*; D006325:Heart Atria; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010539:Permeability; D012433:Ryanodine / Q000494:pharmacology
D012433:Ryanodine; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium