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 alpha1G and alpha1H Ca channels expressed in oocytes with relatively high potency and high selectivity. Here we report its effects on Ca channel currents, carried by 5 mm Ba(2+) 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.
Sidach
Serguei S
SS
Department of Pharmacology and Experimental Therapeutics, Boston University Medical Center, Boston, Massachusetts 02118, USA.
Mintz
Isabelle M
IM
D000818:Animals; D001464:Barium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013788:Thalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020747:Calcium Channels, T-Type; D009498:Neurotoxins; D012604:Scorpion Venoms; C118444:kurtoxin; D001464:Barium