Pertussis toxin treatment blocks hyperpolarization by muscarinic agonists in chick atrium.
Atrial and ventricular adenylate cyclase activity and atrial membrane potentials were measured in hearts from hatched chicks at 2-3 days after intravenous administration of pertussis toxin (0.5-1.0 micrograms, total) or saline. Both in atrium and ventricle, treatment with pertussis toxin antagonized inhibition by carbachol of basal and isoproterenol-stimulated adenylate cyclase activity without changing either basal or isoproterenol-stimulated adenylate cyclase. In atria from pertussis toxin-treated animals (5.4 mM potassium), carbachol hyperpolarized the resting membrane by 0.3 +/- 0.3 mV (n = 9) and did not increase resting potassium conductance. In contrast, carbachol hyperpolarized the resting membrane by 4.5 +/- 0.8 mV (n = 11) and increased resting potassium conductance more than 4-fold in saline-treated animals. Carbachol did not significantly affect the atrial action potential peak or duration at 50% repolarization of pertussis toxin-treated animals. This muscarinic agonist reduced action potential peak by 7.8 +/- 1.2 mV and the duration at 50% repolarization by 22.1 +/- 3.0 msec in atria from saline-treated animals. Pertussis toxin treatment also prevented the negative inotropic effect and the inhibition of calcium-dependent action potentials caused by carbachol in atrial muscle. Neither the affinity nor the maximal specific binding of [3H]quinuclidinyl benzilate in ventricular homogenates was changed by pertussis toxin treatment. The apparent affinity of carbachol for muscarinic receptor was slightly (approximately 2-fold) diminished in pertussis toxin-treated animals. The inhibition of carbachol-induced hyperpolarization by pertussis toxin treatment implicates a guanosine 5'-triphosphate-dependent protein (Ni or a similar protein) as an essential link that permits muscarinic receptor to regulate atrial potassium channels.
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Sorota
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Tsuji
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Tajima
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Pappano
D000200:Action Potentials / Q000187:drug effects; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002645:Chickens; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D007473:Ion Channels; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D002217:Carbachol; D037342:Pertussis Toxin; D011188:Potassium