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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Perrier
M L
ML
Synthelabo Recherche (L.E.R.S.), Biology Department, Bagneux, France.
Scatton
B
B
Benavides
J
J
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D016257:Fura-2 / Q000378:metabolism; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D011189:Potassium Chloride; D002118:Calcium; D016257:Fura-2