Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons.
Capsaicin (CAP), a neurotoxin, has been reported to activate a nonselective cation current in dorsal root ganglion (DRG) neurons. In this paper, we identify and describe the properties of CAP-activated single channels in cultured neonatal rat DRG neurons. We first identified CAP-sensitive whole-cell currents that reversed near 0 mV in physiological solution. In solution containing 140 mM Na+, extracellular application of CAP to outside-out patches caused activation of an ion channel in a concentration-dependent manner (EC50 = 1.1 microM). The channel was blocked by the CAP antagonist capsazepine (10 microM). The channel was also activated by 2-10 nM resiniferatoxin, a potent analog of CAP. In symmetrical 140 mM Na+, the single-channel slope conductances were 45.3 +/- 1.0 and 80.0 +/- 4.2 pS at -60 and +60 mV, respectively, showing outward rectification (n = 9). The reversal potential did not shift significantly when Na+ was replaced by K+, Cs+, Rb+, or Li+, showing that the channel discriminated poorly among cations. The channel was also permeable to Ca2+. Although acid (pH < 6.2) was suggested to be an endogenous activator of the CAP receptor, an acid solution (pH 5.9-6.0) failed to activate the channels in outside-out patches. This is the first clear demonstration of the presence of the CAP-activated ion channel in DRG neuron. Opening of these ligand-gated, cation-selective channels gives rise to the whole-cell CAP-activated current in DRG neurons and may underlie the neurotoxic effects of CAP.
Oh
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U
Section of Physiology, College of Pharmacy, Seoul National University, Korea.
Hwang
S W
SW
Kim
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D000143:Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats
D000143:Acids; D002412:Cations; D004224:Diterpenes; D007473:Ion Channels; D009498:Neurotoxins; C024353:resiniferatoxin; C071423:capsazepine; D002211:Capsaicin