Different regulation of myofilament Ca2+ sensitivity in beta-escin-skinned cardiac and vascular smooth muscles.
We compared the effects of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS, an activator of G-protein), phorbol 12,13-dibutylate (PDB, an activator of protein kinase C) and pimobendan (an inotropic agent with Ca2+-sensitizing action) on the Ca2+ sensitivity of the contractile proteins in beta-escin-skinned muscle preparations obtained from rabbit left ventricles and mesenteric arteries. After the skinning procedure, when GTPgammaS (100 microM) or PDB (1 microM) was added to the Ca2+ solutions, pCa50 were significantly increased in preparations obtained from vascular smooth muscle, but not from cardiac muscle, indicating that G-protein- and protein kinase C-mediated direct Ca2+ sensitization may occur only in smooth muscle, but not in cardiac muscle. In contrast, pimobendan (50 microM) increased the Ca2+ responsiveness only in cardiac muscle. Therefore, we conclude that, in addition to the common regulatory factors affecting Ca2+ sensitivity such as intracellular pH and phosphorylation by protein kinase A, there are other means of regulation of Ca2+ sensitivity working differently in cardiac and in vascular smooth muscles.
Tomita
F
F
Department of Cardiovascular Medicine and Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. cvstaf@med.hokudai.ac.jp
Hattori
Y
Y
Kanno
M
M
Kohya
T
T
Sasaki
M
M
Kitabatake
A
A
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D004928:Escin; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D006652:Histological Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology; D011817:Rabbits
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D015240:Phorbol 12,13-Dibutyrate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004928:Escin; D011493:Protein Kinase C; D002118:Calcium