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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Function
  • Autonomic Nervous System / physiology*
  • Calcium Channels, N-Type / drug effects
  • Calcium Channels, N-Type / genetics
  • Calcium Channels, N-Type / physiology*
  • Electrocardiography
  • Heart Atria / innervation
  • Heart Rate / physiology*
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Myocardial Contraction*
  • omega-Agatoxin IVA / pharmacology


  • Calcium Channels, N-Type
  • omega-Agatoxin IVA
  • voltage-dependent calcium channel (P-Q type)