Autonomic modulation of action potential and tension in guinea pig papillary muscles
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The effects of α1-adrenoceptor and muscarinic acetylcholine receptor stimulation on action potential and tension were studied in guinea pig papillary muscles obtained from both right and left ventricles. Stimulation of muscarinic acetylcholine receptors with carbachol produced a reduction of the action potential duration and a positive inotropic effect in papillary muscles from both ventricles. Both effects were concentration dependent and atropine sensitive. However, differential responsiveness was found upon α1-adrenoceptor activation in muscles obtained from left and right ventricles. In right side papillary muscles, the α1-adreneceptor agonist, methoxamine, decreased the action potentail duration and produced a positive inotropic effect. In contrast, methoxamine decreased the action potential duration but failed to produce a positive inotropic effect in left side papillary muscles. All methoxamine effects were antagonized by prazosin. Responses to maximum concentration of carbachol and methoxamine on the action potential duration and contractility were additive in right side papillary muscles. Phorbol 12,13-dibutyrate (PDB), a direct protein kinase C activator, also decreases the action potential duration in a manner that was additive to both carbachol and methoxamine. However, PDB reversed the positive inotropic effect of carbachol indomethacin and nordihydroguaiaretic acid, blockers of arachidonic acid metabolism, but not by the protein kinase C antagonist, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). These results demonstrate (1) a side-dependent effect of methoxamine, and not carbachol, on muscle contraction, (2) additivity of the effects of α1-adrenoceptor and muscarinic acetylcholine receptor activation on the action potential duration and tension, and (3) that these receptor-mediated effects may involve different second messenger system and/or distinct substrate pools. © 1994.
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Arachidonic acid metabolism; Cardiac action potential; Muscarinic acetylcholine receptor; Positive inotropic effect; Protein kinase C; α1-Adrenoceptor 1 (5 isoquinolinesulfonyl) 2 methylpiperazine; alpha 1 adrenergic receptor; alpha 1 adrenergic receptor stimulating agent; carbachol; enzyme activator; indometacin; methoxamine; muscarinic receptor; nordihydroguaiaretic acid; phorbol dibutyrate; prazosin; protein kinase c activator; protein kinase c inhibitor; animal tissue; arachidonic acid metabolism; article; autonomic nervous system; concentration response; controlled study; drug antagonism; guinea pig; heart left ventricle; heart muscle potential; heart muscle tension; heart papillary muscle; heart right ventricle; nonhuman; priority journal; second messenger; 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine; Acetylcholine; Action Potentials; Animal; Arachidonic Acid; Guinea Pigs; In Vitro; Indomethacin; Isoquinolines; Myocardial Contraction; Papillary Muscles; Piperazines; Protein Kinase C; Receptors, Adrenergic, alpha-1; Receptors, Muscarinic; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
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