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Kurtoxin, A Gating Modifier of Neuronal High- and Low-Threshold Ca Channels

Studies of Ca channels expressed in oocytes have identified kurtoxin as a promising tool for functional and structural studies of low-threshold T-type Ca channels. This peptide, isolated from the venomous scorpion Parabuthus transvaalicus, inhibits low-threshold α1G and α1H Ca channels expressed in oocytes with relatively high potency and high selectivity. Here we report its effects on Ca channel currents, carried by 5 mmBa2+ ions, in rat central and peripheral neurons. In thalamic neurons 500 nm kurtoxin inhibited T-type Ca channel currents almost completely (90.2 ± 2.5% at −85 mV;n = 6). Its selectivity, however, was less than expected because it also reduced the composite high-threshold Ca channel current recorded in these cells (46.1 ± 6.9% at −30 mV;n = 6). In sympathetic and thalamic neurons, 250–500 nm kurtoxin partially inhibited N-type and L-type Ca channel currents, respectively. It similarly reduced the high-threshold Ca channel current that remains after a blockade of P-type, N-type, and L-type Ca channels in thalamic neurons. In contrast, kurtoxin facilitated steady-state P-type Ba currents in Purkinje neurons (by 34.9 ± 3.7%; n = 10). In all cases the kurtoxin effect was voltage-dependent and entailed a modification of channel gating. Exposure to kurtoxin slowed current activation kinetics, although its effects on deactivation varied with the channel types. Kurtoxin thus appears as a unique gating-modifier that interacts with different Ca channel types with high affinity. This unusual property and the complex gating modifications it induces may facilitate future studies of gating in voltage-dependent ion channels.