Intracellular endocardial calcium and myocardial function in rat hearts.
Analyses of [Ca2+]i in the isolated beating rat heart (using Indo-1 dye) demonstrated a direct relationship between developed pressure and each of the following: (a) systolic [Ca2+]i; (b) amplitude of [Ca2+]i transients; and (c) diastolic level of [Ca2+]i. Agents which increased cAMP levels, augmented amplitude of [Ca2+]i transients, and lowered the resting level of [Ca2+]i, thereby shifting the relationship between developed pressure and diastolic as well as systolic [Ca2+]i concentrations towards lower [Ca2+]i levels for comparable peak systolic pressure measurements at constant end-diastolic pressure. Addition of adenosine to the perfusate containing isoproterenol completely prevented any cAMP-induced cytosolic changes. Interventions which altered [Ca2+]i and developed pressure, but did not increase cAMP (e.g., perfusion pressure, extracellular calcium, calcium entry blockers, and alpha agonist), caused an increase in diastolic levels of [Ca2+]i commensurate with the augmentation in developed pressure and amplitude of [Ca2+]i transients. When the diastolic [Ca2+]i rose to 400 nmoles and the cAMP was below 4 nmoles the heart fibrillated. The heart fibrillated at a diastolic [Ca2+]i of 350 nmoles when the cAMP was elevated to 6 nmoles. The diastolic level of [Ca2+]i at which the heart begins to fibrillate is indicative of the effect contraction threshold.
Wikman-Coffelt
J
J
Department of Medicine, University of California, San Francisco.
Wu
S T
ST
Parmley
W W
WW
D000241:Adenosine / Q000494:pharmacology; D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003971:Diastole; D004699:Endocardium / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D015290:Second Messenger Systems; D013599:Systole; D014700:Verapamil / Q000494:pharmacology
D014700:Verapamil; D000242:Cyclic AMP; D000676:Amrinone; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine