Low- and high-voltage-activated calcium currents in rat spinal dorsal horn neurons.
1. Calcium currents in immature rat spinal dorsal horn neurons in transverse slices were studied with the single-electrode voltage-clamp technique. Using experimental conditions that minimized voltage-dependent Na+ and K+ currents, we distinguished low- and high-voltage-activated calcium currents on the basis of their voltage dependence and sensitivity to the Ca2(+)-channel agonist and antagonist drugs. 2. The low-voltage-activated transient calcium current is evoked with weak depolarizing voltage commands. It begins to activate at potentials positive to -70 mV and increases in amplitude and rate of decay with depolarization, the peak values being reached between -40 and -30 mV. The current is fully activated at a holding potential of about -110 mV. Steady-state inactivation is complete at potentials in the range of -60 to -50 mV. 3. The transient component of the high-threshold calcium current appears at membrane potentials close to -40 mV and slowly decays within several hundreds of milliseconds. The amplitude of the current increases with more negative holding potentials (-100 to -40 mV). 4. The sustained component of the high-threshold calcium current seems to activate at potentials positive to -40 mV and exhibits little inactivation during 0.3- to 0.5-s depolarizing commands. This component is better isolated at more depolarized holding potentials (between -40 and -30 mV) that inactivate the transient components of the low- and high-threshold calcium currents. 5. A rundown of calcium currents was seen in dorsal horn cells. The time stability of the transient and sustained components of the high-threshold calcium current was lower than that of the low-threshold transient current. The latter current seemed to be insensitive up to 1 h. 6. (-)-Bay K 8644 (1-10 microM), a dihydropyridine agonist, enhanced the high-threshold calcium current, in particular the sustained component, but not the transient low-threshold calcium current. The dihydropyridine antagonist nifedipine (5-50 microM) selectively reduced the sustained component of the high-threshold calcium current while having little or no effect on the transient components of the low- and high-threshold calcium currents. 7. Cadmium ions (60-100 microM) and cobalt ions (2 mM) markedly reduced both components of the high-threshold calcium current, and Cd2+ only slightly decreased the low-threshold transient current. However, all three components are indiscriminately blocked by higher concentrations of Cd2+ and Co2+.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D002104:Cadmium; D013373:Substance P; D003035:Cobalt; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009532:Nickel