Calcium-induced inotropy is in part mediated by protein kinase C.
Protein kinase C (PKC) is an ubiquitous regulatory enzyme with dense myocardial distribution and activity; however, its physiologic relevance to myocardial function remains poorly understood. Although endogenous Ca2+ is a potent stimulus of PKC isoforms alpha and beta (cPKCs) it remains unknown whether exogenous Ca2+ activates these PKC isoforms, and if so, whether PKC plays any role in Ca2+-induced myocardial inotropy. To study this, ventricular sections from isolated rat hearts, with and without Ca2+-induced inotropy (CaCl2, 0.5 mM coronary concentration x 2 min), were probed for cPKC isoform translocation using immunofluorescence in order to determine if exogenous Ca2+ indeed activates cPKCs. We further examined the effects of exogenous Ca2+, with and without concurrent PKC inhibition (chelerythrine, 20 microM coronary concentration x 2 min), on fundamental physiologic parameters of myocardial developed pressure (DP), dP/dt, and coronary flow (CF) in the isolated rat heart to determine if Ca2+-induced inotropy involves PKC. Results indicated that exogenous Ca2+ results in translocation of PKC a from the cytoplasm to the sarcolemma and intercalated discs, as well as the translocation of PKC beta from the perinuclear to the intranuclear compartment. This dose of exogenous Ca2+ resulted in myocardial inotropy as determined by DP, dP/dt, and CF. Furthermore, myocardial inotropy was attenuated with concurrent inhibition of PKC activity. These findings link the physiologic effects of exogenous Ca2+ to PKC, providing a better understanding of the physiologic mechanism of Ca2+-induced inotropy.
Meldrum
D R
DR
Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Cleveland
J C
JC
Rowland
R T
RT
Banerjee
A
A
Harken
A H
AH
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004789:Enzyme Activation; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology*; D011312:Pressure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D011493:Protein Kinase C; D002122:Calcium Chloride; D002118:Calcium