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J Neurophysiol 95: 2698-2704, 2006. First published December 28, 2005; doi:10.1152/jn.01221.2005
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Compensatory Contribution of Cav2.3 Channels to Acetylcholine Release at the Neuromuscular Junction of Tottering Mice

Simon Kaja1,2, Rob C. G. Van de Ven3, Michel D. Ferrari1, Rune R. Frants3, Arn M.J.M. Van den Maagdenberg1,3 and Jaap J. Plomp1,2

1Departments of Neurology, 2Molecular Cell Biology-Group Neurophysiology, and 3Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands

Submitted 18 November 2005; accepted in final form 21 December 2005

Tottering (Tg) mice carry the mutation P601L in their Cacna1a encoded Cav2.1 channels. Transmitter release at the wild-type neuromuscular junction (NMJ) is almost exclusively mediated by Cav2.1 channels, and we used this model synapse to study synaptic consequences of the Tg mutation. With electrophysiology, and using subtype-specific Cav2 channel-blocking toxins, we assessed a possible compensatory contribution of non-Cav2.1 channels to evoked acetylcholine (ACh) release at Tg NMJs. Release was reduced by ~75% by the Cav2.1 channel blocker {omega}-agatoxin-IVA, which was less than the ~95% reduction observed in wild-type. Release at Tg NMJs, but not at wild-type synapses, was reduced by ~15% by SNX-482, a Cav2.3 channel blocker. No Cav2.2 channel involvement was found. Probably, there is a small reduction in functional presynaptic Cav2.1 channels at Tg NMJs, which is compensated for by Cav2.3 channels. The remaining Cav2.1 channels are likely to convey enlarged Ca2+ flux, because evoked ACh release at Tg NMJs, at low extracellular Ca2+ concentration, was approximately sixfold higher than at wild-type NMJs. This is the first report of compensatory expression of non-Cav2.1 channels at NMJs of mice with a single amino acid change in Cav2.1.

Address for reprint requests and other correspondence: J. J. Plomp, Dept. of Molecular Cell Biology-Group Neurophysiology, Research Building, Leiden University Medical Centre, PO Box 9600, NL-2300 RC Leiden, The Netherlands (E-mail: j.j.plomp{at}lumc.nl)




This article has been cited by other articles:


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 J. Pharmacol. Exp. Ther.Home page
N. E. Pardo, R. K. Hajela, and W. D. Atchison
Acetylcholine Release at Neuromuscular Junctions of Adult Tottering Mice Is Controlled by N-(Cav2.2) and R-Type (Cav2.3) but Not L-Type (Cav1.2) Ca2+ Channels
J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1009 - 1020.
[Abstract] [Full Text] [PDF]


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