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Keywords:

  • Ca2+ channels;
  • motoneuron;
  • neurotransmission;
  • SNX-482;
  • spinal cord

Abstract

Molecular studies have revealed the presence of R-type voltage-gated Ca2+ channels at pre- and postsynaptic regions; however, no evidence for the participation of these channels in transmitter release has been presented for the spinal cord. Here we characterize the effects of SNX-482, a selective R channel blocker, on the monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in motoneurons by stimulation of dorsolateral funiculus (DLF) terminals in a slice preparation from the adult turtle spinal cord. SNX-482 inhibited neurotransmission in a dose-dependent manner, with an IC50 of ∼9 ± 1 nM. The EPSP time course and membrane time constant of the motoneurons were not altered, suggesting a presynaptic mechanism. The toxin inhibited the residual component of the EPSPs recorded in the presence of N- and P/Q-type Ca2+ channel blockers, strongly suggesting a role for the R channels in neurotransmission at the spinal cord DLF terminals. Consistently with this, RT-PCR analysis of turtle spinal cord segments revealed the expression of the CaV2.3 pore-forming (α1E) subunit of R channels, whereas the use of anti-α1E-specific antibodies resulted in its localization in the DLF fibers as demonstrated by immunohistochemistry coupled with laser confocal microscopy. J. Comp. Neurol. 513:188–196, 2009. © 2009 Wiley-Liss, Inc.