Dihydropyridine- and omega-conotoxin-resistant, neomycin-sensitive calcium channels mediate the depolarization-induced increase in internal calcium levels in cortical slices from immature rat brain
In order to characterize pharmacologically voltage-operated calcium channels in the rat brain, we have developed a technique to measure intracellular calcium levels ([Ca++]i) in immature rat cortical slices loaded with the fluorescent calcium probe Fura-2. KCl depolarization caused a rapid and rever...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 261; no. 1; pp. 324 - 330 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.04.1992
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Subjects | |
Online Access | Get full text |
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Summary: | In order to characterize pharmacologically voltage-operated calcium channels in the rat brain, we have developed a technique
to measure intracellular calcium levels ([Ca++]i) in immature rat cortical slices loaded with the fluorescent calcium probe
Fura-2. KCl depolarization caused a rapid and reversible increase in cortical [Ca++]i. A significant increase was already
observed at 20 mM KCl and the maximal effect was obtained at 77 mM. This response was not modified when extracellular Na+
was substituted by the nonpermeant cation bis(2-hydroxyethyl)-dimethylammonium chloride and was insensitive to the Na+ channel
blocker tetrodotoxin (1 microM). In the absence of extracellular Ca++, KCl (50 mM) failed to increase [Ca++]i. The KCl (50
mM)-induced increase in [Ca++]i was not affected by the L-type calcium channel blockers nifedipine and isradipine and was
only partially inhibited (by less than 30% at 50 microM) by verapamil and diltiazem. In contrast, nimodipine prevented this
response by 41% at 50 microM. Flunarizine (a nonselective T channel blocker) inhibited the KCl response by 47% at 30 microM,
whereas nicergoline (another nonselective T channel blocker) reduced this entry by 74% at 300 microM (IC50 = 120 microM).
Cyclandelate, an atypical calcium antagonist, inhibited KCl-induced increase in [Ca++]i with a maximal effect of 41% at 30
microM, whereas perhexiline was inactive. The KCl-induced rise in [Ca++]i was only marginally inhibited by omega-conotoxin
with a maximal effect of 20% from 1 nM to 1 microM. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3565 1521-0103 |