Endothelin-1 raises excitability and reduces potassium currents in sensory neurons.

Exposure to endothelin-1 (ET-1, 50 nM) of sensory neurons, acutely isolated from rat dorsal root ganglia (DRG), results in an increase in the number of action potentials elicited by a linear ramp of stimulating current. The changes are complete in 5 min after ET-1 treatment and do not reverse in 5-10 min after ET-1's removal. Neither the resting potential, nor the threshold potential for the first or second action potentials, nor their rate-of-rise or decay, are changed by ET-1 exposure, but the slow depolarizations which occur before the first and second action potentials during the current ramp are increased by ca. 50% by ET-1. The delayed rectifier type of K(+) currents (I(K)), measured under whole-cell voltage clamp, are depressed by approximately 30% during such exposure to ET-1. The voltage-dependent gating of steady-state I(K) and the current kinetics are unchanged by ET-1, leaving the sole effect as a drop in the number of available channels. I(K) is affected by ET-1 only in Isolectin B(4)-positive cells, suggesting that there may be a selective action in enhancing impulse activity on this class of nociceptive neuron. This decrease in I(K) will potentiate the excitability-inducing actions of the previously reported negative shift in tetrodotoxin-resistant Na(+) channel gating in such neurons.