Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons

Abstract

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 μM). The channel was blocked by the CAP antagonist capsazepine (10 μM). 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) tailed 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.