RT Journal Article
SR Electronic
T1 Zebrafish Calls for Reinterpretation for the Roles of P/Q Calcium Channels in Neuromuscular Transmission
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7384
OP 7392
DO 10.1523/JNEUROSCI.5839-12.2013
VO 33
IS 17
A1 Wen, Hua
A1 Linhoff, Michael W.
A1 Hubbard, Jeffrey M.
A1 Nelson, Nathan R.
A1 Stensland, Donald
A1 Dallman, Julia
A1 Mandel, Gail
A1 Brehm, Paul
YR 2013
UL http://www.jneurosci.org/content/33/17/7384.abstract
AB A long-held tenet of neuromuscular transmission is that calcium-dependent neurotransmitter release is mediated by N-type calcium channels in frog but P/Q-type channels in mammals. The N-type assignment in frog is based principally on pharmacological sensitivity to ω-conotoxin GVIA. Our studies show that zebrafish neuromuscular transmission is also sensitive to ω-conotoxin GVIA. However, positional cloning of a mutant line with compromised neuromuscular function identified a mutation in a P/Q- rather than N-type channel. Cloning and heterologous expression of this P/Q-type channel confirmed a block by ω-conotoxin GVIA raising the likelihood that all vertebrates, including frog, use the P/Q-type calcium channel for neuromuscular transmission. In addition, our P/Q defective mutant line offered a means of testing the ability of roscovitine, known to potentiate frog neuromuscular transmission, to mediate behavioral and functional rescue. Acute treatment led to rapid improvement of both, pointing to potential therapeutic benefit for myasthenic disorders involving calcium channel dysfunction.