Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents

Journal of Neurophysiology
S M Todorovic, C J Lingle

Abstract

We have used the whole cell patch-clamp method to study pharmacological properties of low-voltage-activated (LVA) Ca2+ current in freshly dissociated neurons from dorsal root ganglia of adult rats. Inward barium current [in the presence of internal fluoride to reduce L-type high-voltage-activated (HVA) and external 1 microM omega-conotoxin GVIA to block N-type HVA current- was evoked from negative holding potentials of -90 mV to test potentials of -25 mV and showed complete inactivation during 200-ms test pulses. Amiloride blocked approximately 90% of current with half-maximal block (EC50) of 75 microM and a Hill coefficient (n) of 0.99. LVA current was blocked completely by inorganic Ca2+ channel blockers: lanthanum (EC50 = 0. 53 microM) > zinc (EC50 = 11.3 microM) > cadmium (EC50 = 20 microM)> nickel (EC50 = 51 microM). The antiepileptics, ethosuximide (EC50 = 23.7 mM, n = 1.4), phenytoin (EC50 = 7.3 microM, n = 1.3), alpha-methyl-alpha-phenylsuccinimide (EC50 = 170 microM, n = 2.1), and valproic acid (EC50 = 330 microM, n = 1.9) maximally blocked approximately 100, 60, 26, and 17% of T current, respectively. Another antiepileptic, carbamazepine (</=100 microM), and convulsants such as pentylenetetrazole (1 mM) and tert-butyl...Continue Reading

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Citations

Feb 4, 1999·Journal of Neurochemistry·M E WilliamsK A Stauderman
Nov 17, 2001·The Journal of Physiology·R BournaudT Shimahara
Sep 13, 2003·British Journal of Pharmacology·Slobodan M TodorovicVesna Jevtovic-Todorovic
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Mar 1, 2007·American Journal of Physiology. Endocrinology and Metabolism·Seung-Kwon YangChen Chen
Dec 14, 2007·Annals of the New York Academy of Sciences·Pavle M JoksovicSlobodan M Todorovic
Jul 17, 2010·Annals of the New York Academy of Sciences·Pavle M Joksovic, Slobodan M Todorovic
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