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.
Feng
Bihua
B
Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Strichartz
Gary
G
D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000166:cytology / Q000502:physiology*; D013997:Time Factors; D053675:Versicans
D051668:Delayed Rectifier Potassium Channels; D019332:Endothelin-1; D006023:Glycoproteins; D037102:Lectins; C508324:Vcan protein, rat; D053675:Versicans; D011188:Potassium