title: Muscarinic agonist-induced positive inotropic response in chick atria.
abstract: Carbachol (10(-6)-3X10(-4)M) induces a positive inotropic response in paced, pertussis toxin-treated fibers which is atropine-sensitive and independent of endogenous catecholamines. At the same concentrations in atria from saline-treated chicks, carbachol's negative inotropic effect on the steady state contractions (SSC) is attenuated and the rested state contraction (RSC) is increased. The RSC and SSC in pertussis toxin-treated fibers are increased by carbachol (EC50 = 30 microM) indicating that repetitive electrical depolarization is not essential for the inotropic response. The inotropic response of the SSC is frequency-independent from 0.10-1.0 Hz; however it is decreased (approximately 50%) at a high frequency (3.0 Hz). In control untreated atrial muscle, carbachol (10(-4)M) selectively increases the early component of the RSC. The late component of the RSC, representing activation of transmembrane Ca2+ inward current, is not changed. Carbachol's positive inotropic effect is perhaps exerted by enhancing Ca2+ release and/or Ca2+ content of the sarcoplasmic reticulum. The ability of various muscarinic agonists to induce a positive inotropic response was: carbachol > acetylcholine > oxotremorine. This order correlates with the ability of these agents to induce a tetrodotoxin-resistant Na+ inward current that increases intracellular Na+ and to promote phosphatidylinositol hydrolysis. These data are consistent with the hypothesis that the carbachol-induced positive inotropic response may result from greater intracellular Ca2+ availability secondary to enhanced Na-Ca exchange. The greater Ca2+ availability, together with increased production of the Ca-mobilizing messenger, inositol 1,4,5-trisphosphate (InsP3), can exert a synergistic effect to regulate force generation.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D018721:Muscarinic Agonists; D010566:Virulence Factors, Bordetella; D015240:Phorbol 12,13-Dibutyrate; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D012964:Sodium; D037342:Pertussis Toxin; D002118:Calcium