Modified autonomic regulation in mice with a P/Q-type calcium channel mutation.
Recent genetic analyses revealed an important association between P/Q-type channels and hereditary neurological disorders. The alpha1 subunit of P/Q-type channels is coded by a single CaV2.1 gene. Since calcium entry via neuronal calcium channels is essential for neurotransmission, P/Q-type channels may play an important role in cardiac autonomic neurotransmission. To elucidate the physiological importance of P/Q-type channels in autonomic nerve control, we used rolling Nagoya (tg(rol)) mice, which have a mutation in the CaV2.1 gene and decreased P/Q-type channel currents with reduced voltage sensitivity. The tg(rol) mice demonstrated unmodified expression of other calcium channel subunits. Electrocardiogram and echocardiographic analyses revealed decreased heart rate. Furthermore, omega-agatoxin IVA, a P/Q-type channel inhibitor, decreased heart rate and ejection fraction only in wild-type mice, thus suggesting a significant involvement of P/Q-type channels in chronotropic regulation. Atrium contraction analyses revealed a minor but significant role for P/Q-type channels in sympathetic and parasympathetic nerve regulation.
Department of Physiology, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan.
Takayoshi
T
Ohba
Eiki
E
Takahashi
Manabu
M
Murakami
D000818:Animals; D016275:Atrial Function; D001341:Autonomic Nervous System / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004562:Electrocardiography; D006325:Heart Atria / Q000294:innervation; D006339:Heart Rate / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009200:Myocardial Contraction; D020867:omega-Agatoxin IVA / Q000494:pharmacology
D020864:Calcium Channels, N-Type; D020867:omega-Agatoxin IVA