Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin

The biophysical properties of T-type voltage-gated calcium channels are well suited to pacemaking and to supporting calcium flux near the resting membrane potential in both excitable and nonexcitable cells. We have identified a new scorpion toxin (kurtoxin) that binds to the alpha(1G) T-type calcium channel with high affinity and inhibits the channel by modifying voltage-dependent gating. This toxin distinguishes between alpha(1G) T-type calcium channels and other types of voltage-gated calcium channels, including alpha(1A), alpha(1B), alpha(1C) and alpha(1E). Like the other alpha-scorpion toxins to which it is related, kurtoxin also interacts with voltage-gated sodium channels and slows their inactivation. Kurtoxin will facilitate characterization of the subunit composition of T-type calcium channels and help determine their involvement in electrical and biochemical signaling.