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KMID : 0880520070430030158
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Chonnam Medical Journal
2007 Volume.43 No. 3 p.158 ~ p.167
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The Effect of DA-5018, A Synthetic Capsaicin Derivative, on Voltage-Dependent Calcium Currents in Trigeminal Ganglion Neurons of Neonatal Rats
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Kim Joon-Sung
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Abstract
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Capsaicin is known to produce initial excitation followed by desensitization to various stimuli on the sensory neurons. The aim of this study was to investigate the electrophysiological characteristics of voltage-dependent calcium currents (ICa) in trigeminal ganglion (TG) neurons of neonatal rats, and the effect of DA-5018, a synthetic water-soluble capsaicin derivative, on the ICa in vitro using a whole cell patch-clamp technique. TG neurons were acutely isolated into single cells from Sprague-Dawley rats. Sixty two cells out of 68 cells displayed high-voltage activated (HVA) ICa, the rest of them did low-voltage activated (LVA or T-type) ICa. In most DA-5018-sensitive subpopulation of TG neurons (70%), the magnitude of HVA ICa was markedly inhibited by DA-5018 in a dose-dependent manner. The inhibition of DA-5018 on ICa was greater at basic pH than at physiological pH. DA-5018-induced inhibition of voltage-dependent ICa was reversibly blocked by pretreatment with ruthenium red, a non-competitive antagonist of vanilloid receptor. These results suggest that there are LVA and HVA Ca2+ channels including N and L type in small-sized TG neurons of neonatal rats, and that HVA ICa are more sensitive to DA-5018 than LVA ICa. DA-5018 inhibits voltage-dependent ICa in dose- and pH-dependent manner, possibly through the activation of vanilloid receptors.
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KEYWORD
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DA-5018, Capsaicin, Vanilloid receptor, Calcium channel, Trigeminal ganglion
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