Acetylcholine inhibition in rabbit sinoatrial node is prevented by pertussis toxin.
The effects of acetylcholine (ACh) were examined on the naturally occurring slow action potentials (APs) of the isolated, organ-cultured, spontaneously beating sinoatrial (SA) node of the rabbit, in the presence or absence of pertussis toxin. The sensitivity of the SA-node preparations to ACh was not altered after 24 h incubation in organ culture medium. Activation of the muscarinic receptor hyperpolarized the cells and reduced the frequency of spontaneous activity at low concentrations (1 X 10(-6) and 3 X 10(-6) M), and completely abolished automaticity at higher concentrations (1 X 10(-5) M). However, stimulated activity was maintained. Increased concentrations (1 X 10(-4) M) of ACh completely abolished excitability. When the SA-node preparations were cultured in the presence of 0.5 micrograms/mL pertussis toxin, concentrations of ACh as high as 1 X 10(-4) M had no effect on the AP parameters and frequency of spontaneous activity. The results indicate that inactivation of G proteins by pertussis toxin caused inhibition of the ACh effects on the automaticity of the SA node. In addition, the blocking effect of ACh to the naturally occurring slow APs was also inhibited by pertussis toxin. We conclude that in the rabbit SA node, the effects of ACh on automaticity and on the slow channels are mediated by G protein.
Molyvdas
P A
PA
Department of Physiology and Biophysics, College of Medicine, University of Cincinnati, OH 45267-0576.
Sperelakis
N
N
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects; D009924:Organ Culture Techniques; D037342:Pertussis Toxin; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D000109:Acetylcholine