Subconductance behavior in a maxi Ca2(+)-activated K+ channel induced by dendrotoxin-I.
Toxin I (DTX-I), a 60-residue peptide belonging to the dendrotoxin family of Mamba snake neurotoxins, is a potent inhibitor of various types of voltage-gated K+ currents. To investigate the sensitivity of another major class of K+ channels to DTX-I, the effect of this toxin was studied on single Ca2(+)-activated K+ channels from rat skeletal muscle incorporated into planar bilayers. Internal (intracellular) DTX-I was found to induce reversibly a long-lived (tau = 40 s), inwardly rectifying subconductance state with 66% of the normal open-state current at +20 mV. Analysis of the kinetics of substate formation and the current-voltage behavior of the substate suggest that binding of DTX-I modifies conduction of K+ ions through the pore without affecting the Ca2+ dependence or voltage dependence of gating. These results identify a unique internal binding site for DTX-I (Kd = 90 nM in 50 mM KCl) on a ubiquitous class of high-conductance, Ca2(+)-activated K+ channels.
Lucchesi
K
K
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Moczydlowski
E
E
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology*; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D009132:Muscles / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D012910:Snake Venoms
D004546:Elapid Venoms; D009498:Neurotoxins; D015221:Potassium Channels; D012910:Snake Venoms; C020273:dendrotoxin; D002118:Calcium