Linked Life Data

9425195

Source:http://linkedlifedata.com/resource/pubmed/id/9425195

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-2-18
pubmed:abstractText
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-bicyclo [2.2.2] phosphorothionate (50 microM) had no effect on T current. Barbiturates completely blocked T current: thiopental (EC50 = 153 microM, n =1.2) > pentobarbital (EC50 = 334 microM, n = 1.2) > methohexital (EC50 = 502 microM, n = 1.3) > phenobarbital (EC50 = 1. 7 mM, n = 1.2). Blockade by thiopental and pentobarbital did not show voltage or use dependence. General anesthetics blocked T current completely and reversibly: propofol (EC50 = 12.9 microM, n = 1.3) > octanol(EC50 = 122 microM, n = 1.2) > etomidate (EC50 = 205 microM, n =1.3) > isoflurane (EC50 = 303 microM, n = 2.3) > halothane (EC50 = 655 microM, n = 2.0) > ketamine (EC50 = 2.5 mM, n = 1.1). Mibefradil, a novel Ca2+ channel blocker, blocked dorsal root ganglion T current in a voltage- and use-dependent fashion with an EC50 of approximately 3 microM (n = 1.3). When compared with results on other T currents, these data indicate that significant differences exist among different T currents in terms of pharmacological sensitivities. Furthermore, differences in pharmacological sensitivity of T currents among peripheral neurons, CNS, and neuroendocrine cells may contribute to the spectrum of effects of particular analgesic, anticonvulsant, and anesthetic drugs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3077
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
240-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents.
pubmed:affiliation
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.