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Journal of Neuroscience, Vol 16, 1659-1667, Copyright © 1996 by Society for Neuroscience
Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons
U Oh, SW Hwang and D Kim
Section of Physiology, College of Pharmacy, Seoul National University, Korea.
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.
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