TY - JOUR T1 - Differential blockade of voltage-sensitive calcium channels at the mouse neuromuscular junction by novel omega-conopeptides and omega-agatoxin-IVA. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 248 LP - 256 VL - 273 IS - 1 AU - S S Bowersox AU - G P Miljanich AU - Y Sugiura AU - C Li AU - L Nadasdi AU - B B Hoffman AU - J Ramachandran AU - C P Ko Y1 - 1995/04/01 UR - http://jpet.aspetjournals.org/content/273/1/248.abstract N2 - This investigation assessed the ability of a variety of calcium channel blocking peptides to block synaptic transmission in the isolated mouse phrenic nerve-hemidiaphragm. The synthetic version of the naturally occurring N-type voltage-sensitive calcium channel (VSCC) blocker omega-conopeptide MVIIA (SNX-111) had no effect on nerve-evoked muscle contractions. The non-N-, non-L-type VSCC blocker, omega-conopeptide MVIIC (SNX-230), blocked neuromuscular transmission completely, as did the selective P-type VSCC blocker, omega-Aga-IVA. Subsequent evaluation of other synthetic omega-conopeptides and analogs disclosed a significant positive correlation between the test compounds' affinities for high-affinity SNX-230 brain binding sites and their neuromuscular blocking potencies. Quantal analysis of transmitter release showed that SNX-230 abolished evoked endplate potentials completely, but had little effect on the amplitude and frequency of spontaneous miniature endplate potentials. Perineural focal recordings of presynaptic currents showed that SNX-230 did not block the neuronal action potential. These and other findings indicated that SNX-230 prevents transmitter release at the mouse neuromuscular junction by blocking calcium channels at presynaptic nerve endings. These calcium channels correspond pharmacologically to VSCCs associated with high-affinity binding sites in rat brain and are most probably either of the P- or Q-type. ER -