Dendrotoxin: a selective blocker of a non-inactivating potassium current in guinea-pig dorsal root ganglion neurones

Abstract

1. The voltage clamp technique was used to study the effects of dendrotoxin (DTX) on outward potassium currents in internally perfused dorsal root ganglion neurones of guinea-pig. Sodium currents were eliminated by tetrodotoxin (TTX, 2 μmol/l), calcium currents and calcium-activated potassium conductances were abolished by intracellular perfusion of cells with KF. 2. Depolarizing voltage shifts from a holding potential of −90 mV yielded a fast transient outward current (I ^f_K ) and a delayed non-inactivating outward current (I K/s). These currents could be separated by shifting the membrane potential to −50 mV, whereI ^f_K was almost completely inactivated. 3. DTX, at concentrations of 0.14–1.4 nmol/l selectively reduced a portion of the non-inactivating potassium current, leaving the transient outward current unaffected. Once manifested, the action of DTX could not be reversed by washing. 4. The I–V characteristic of the current blocked by DTX is almost linear and quite different from the one of the ‘DTX-resistant’ portion ofI ^s_K , which shows a non-linear I–V curve. 5. Tetraethylammonium (TEA, 30 mmol/l) strongly reducedI ^f_K andI ^s_K . However, subsequent application of DTX was still able to further reduceI ^s_K . 6. 3,4-diaminopyridine (3,4-DAP, 500 μmol/l) unselectively reducedI ^f_K and a portion ofI ^s_K . The remainder of the latter could not further be reduced by DTX, suggesting a similar action of the two blockers on non-inactivating potassium currents. 7. From the results presented, it is suggested that dendrotoxin selectively blocks a non-inactivating subtype of potassium channel.