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Biochem Biophys Res Commun. 2009 Mar 27;381(1):27-32. doi: 10.1016/j.bbrc.2009.01.184. Epub 2009 Feb 6.

Modified autonomic regulation in mice with a P/Q-type calcium channel mutation.

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Department of Physiology, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan.


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.

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