Effects of propofol on TTX-sensitive voltage-gated sodium channels in rat acutely dissociated spinal dorsal horn neurons

Abstract

Abstract: AIM: To investigate the effects of propofol on TTX-sensitive voltage-gated sodium currents and its mechanism in acutely dissociated rat spinal dorsal horn neurons.METHODS: Seven-day-old male SD rats were decapitated, a segment of lumbar enlargement of the spinal cord was dissected out, then the dorsal horn neurons were dissociated, and the wholecell patch clamp recording were performed.Propofol of 0.3-30 μmol/L was applied 100 μm apart from the cells.The currents were activated by a 30ms-pulse of-10 mV from holding petential(-80 mV).The inhibitory concentration in 50% of the sodium current amplitude (IC₅₀) value of propofol was estimated.For investigation of sodium channels inactivation, propofol of IC₅₀level was applied, sodium currents were activated by a 30 ms-pulse of 0 mV after a 30 ms-prepulse from-80 mV to-20 mV with a voltage step of 10 mV. For investigation of sodium channels deinactivation, sodium currents were activated by a 30 ms-pulse to-10 mV after a 30 ms-prepulse to-10 mV from holding pontential (-80 mV) under propofol of IC₅₀level, the intervals between the two pulses were from 2 ms to 24 ms.RESULTS: Propofol could inhibit tetrodotoxinsensitive sodium currents in a concentration-dependent manner, the IC₅₀value of propofol was (5.35±0.25) μmol/L.In inactivating sodium channels test, from-60 mV to-40 mV of the prepulse, propofol of IC₅₀level could suppress sodium currents activated by the test pulse significantly (P<0.05);in deinactivating sodium channels test, the currents activated by the test pulse with the intervals from 2ms to 6 ms were significantly suppressed by propofol with IC₅₀ level (P<0.01, P<0.05).CONCLUSION: Propofol inhibited TTX-sensitive voltage-gated sodium currents in rat dorsal horn neurons, which was mediated by facilitating sodium channels inactivating and inhibiting sodium channels from its deinactivation.

Key words: propofol, dorsal horn neuron, sodium current

CLC Number:

R965.2

LIU Hong-liang, GUO Wei-tao, ZENG Yin-ming, YAO Shang-long. Effects of propofol on TTX-sensitive voltage-gated sodium channels in rat acutely dissociated spinal dorsal horn neurons[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(6): 614-619.

References

[1] Light AR, Trevino DL, Perl ER. Morphological features of functionally defined neurones in the marginal zone and substantia gelatinosa of the spinal dorsal horn[J]. J Comp Neurol, 1979, 186(2): 151-171.
[2] Lee Y, Lee CH, Oh U. Painful channels in sensory neurons[J]. Mol Cells, 2005, 20(3): 315-324.
[3] Kim CH, Oh Y, Chung JM, et al. Changes in three subtypes of tetrodotoxin sensitive sodium channel expression in the axotomized dorsal root ganglion in the rat[J]. Neurosci Lett, 2002, 323(2): 125-128.
[4] Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics[J]. N Engl J Med, 2003, 348(21): 2110-2124.
[5] Concas A, Santoro G, Serra M, et al. Neurochemical action of the general anesthetic propofol on the chloride ion channel coupled with the GABAA receptors[J]. Brain Res, 1991, 542(2): 225-232.
[6] Ratnakumari L, Hemmings HC. Effects of propofol an sodium channel-dependent sodium influx and glutamate release in rat cerebrocortical synaptosomes[J]. Anesthesiology, 1997, 86(2): 428-439.
[7] Rehberg B, Duch DS. Suppression of central nervous system sodium channels by propofol[J]. Anesthesiology, 1999, 91(2): 512-520.
[8] Frenkel C, Urban BW. Human brain sodium channels as one of the molecular target sites for the new intravenous anaesthetic propofol (2, 6-diisopropylphenol) [J]. Eur J Pharmacol, 1991, 208(1): 75-79.
[9] Veintemilla F, Elinder F, Arhem P. Mechanisms of propofol action on ion currents in the myelinated axon of Xenopus laevis[J]. Eur J Pharmacol, 1992, 218(1): 59-68.
[10] Kerchner GA, Wilding TJ, Li P, et al. Presynaptic kainite receptors regulate spinal sensory transmission[J]. J Neurosci, 2001, 21(1): 59-66.
[11] Joo DT, Xiong ZG, MacDonald JF, et al. Blocker of glutamate receptors and barbiturate anesthesia: increased sensitivity to pentobarbital-induced anesthesia despite reduced inhibition of AMPA receptors in GluR2 null mutant mice [J]. Anesthesiology, 1999, 91(5): 1329-1341.
[12] Romey G, Chicheportiche R, Lazdunski M. Transition temperatures of the electrical activity of ion channels in the nerve membrane[J]. Biochim Biophys Acta, 1980, 602 (3): 610-620.
[13] Li P, Wilding TJ, Kim SJ, et al. Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord[J]. Nature, 1999, 397(6715): 161-164.
[14] Kimura M, Sawada K, Miyagawa T, et al. Role of glutamate receptors and voltage-dependent calcium and sodium channels in the extracellular glutamate/aspartate accumulation and subsequent neuronal injury induced by oxygen/glucose deprivation in cultured hippocampal neurons[J]. J Pharmacol Exp Therap, 1998, 285(1): 178-185.
[15] Rehberg B, Xiao YH, Duch DS. Central nervous sy stem sodium channels are significantly suppressed at clinical concentrations of volatile anesthetics[J]. Anesthesiology, 1996, 84(5): 1223-1233.
[16] Smith C, McEwan AI, Jhaveri R, et al. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision[J]. Anesthesiology, 1994, 81(4): 820-828.