Biophysical and pharmacological characterization of voltage-sensitive calcium currents in neonatal rat inferior colliculus neurons.
Calcium conductances have been found in neonatal inferior colliculus neurons, however the biophysical and pharmacological profiles of the underlying calcium currents have not yet been characterized. In this study, we examined which types of voltage-activated calcium currents comprise the whole-cell inward current of neonatal inferior colliculus neurons (10-22microm in diameter). On the basis of their voltage-dependence and pharmacological sensitivities, three major components of barium currents were identified. A low threshold voltage-activated current that activated around -70mV, a mid threshold voltage-activated current that activated near -50mV, and a high threshold voltage-activated current that activated around -40mV. Low and mid threshold voltage-activated currents were present in 33% and 41% of the recordings, respectively, whereas high threshold voltage-activated currents were recorded in all inferior colliculus neurons tested. Nickel chloride (50microM) and U-92032 (1microM), which both block low threshold voltage-activated currents, reduced the amplitude of low threshold voltage-activated peak currents at a test potential of -60mV by 72% and 10%, respectively. In addition, 50microM nickel chloride and 1microM U-92032 reduced the amplitude of mid threshold voltage-activated peak currents measured at -20mV by 55% and 21%, respectively. Further pharmacological analysis indicated the presence of multiple types of high threshold voltage-activated currents in neonatal inferior colliculus neurons. The dihydropyridine nimodipine (1microM), a selective L-type current antagonist, reduced the amplitude of high threshold voltage-activated peak currents by 25%. In addition, FPL 64176 (1microM), a non-dihydropyridine L-type current agonist caused a dramatic 534% increase in the amplitude of the slow sustained component of the tail current measured at -40mV. These data indicate that inferior colliculus neurons express L-type channels. omega-Conotoxin GVIA (1microM), a selective blocker of N-type current, inhibited high threshold voltage-activated peak currents by 28% indicating the presence of N-type channels. omega-Agatoxin IVA (300nM), a potent P/Q-type antagonist, reduced high threshold voltage-activated peak currents by 27%, suggesting that inferior colliculus neurons express P/Q-type channels. Concomitant application of nimodipine (1microM), omega-conotoxin GVIA (1microM) and omega-agatoxin IVA (300nM) onto inferior colliculus neurons decreased the control high threshold voltage-activated peak currents only by 62%.Thus, inferior colliculus neurons may express at least one more type of calcium current in addition to low and mid threshold voltage-activated currents and L-type, N-type and P/Q-type high threshold currents.
N'Gouemo
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Department of Physiology and Program in Neuroscience, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA.
Rittenhouse
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D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D004338:Drug Combinations; D005260:Female; D066298:In Vitro Techniques; D007245:Inferior Colliculi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014334:Tropolone / Q000031:analogs & derivatives / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004338:Drug Combinations; D010879:Piperazines; D020867:omega-Agatoxin IVA; C086422:U 92032; D001464:Barium; D009553:Nimodipine; D014334:Tropolone; D009532:Nickel; D020866:omega-Conotoxin GVIA