N-type voltage-sensitive calcium channels (VSCCs) play a key role in modulating pain pathways.It has been demonstrated electrophysiologically that ω-GVIA inhibits (i) partially the excitatory(EPSP) and totally the inhibitory (IPSP) synaptic transmission in CNS neurons, (ii) partially the voltage-dependent calcium currents in bulbospinal neurons of the rostral ventrolateral medulla (RVLM) and (iii) partially the calcium current in neurons of spinal laminae I and II . However, the actions of other ω-conotoxins have not been studied in spinal or brain slice preparations.

We will compare the actions of CVID, MVIIA, GVIA and a number of synthesised analogues in slice preparations to establish if these conopeptides have different effects arising from their differences in calcium channel selectivity. In addition, we will identify analogues of CVID that preferentially inhibit N-type calcium channels in ascending excitatory pathways in the spinal cord over descending inhibitory pathways.










Sequence alignment and Calcium channel selectivity for several conopeptides
* = C-terminal amide