Evidence for multiple types of Ca2+ channels in acutely isolated hippocampal CA3 neurones of the guinea-pig. 1991

D J Mogul, and A P Fox
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.

1. Current through Ca2+ channels was studied in acutely isolated guinea-pig pyramidal neurones from the CA3 region of the hippocampus. Both the whole-cell and single-channel patch-clamp configuration were used. 2. Both whole-cell and single-channel currents displayed holding potential sensitivity indicative of two high-threshold currents similar to L- and N-type Ca2+ currents. 3. A low-threshold whole-cell current, similar to T-type current seen in dorsal root ganglion (DRG) neurones, activated at -60 to -50 mV and was blocked by nickel (100 microM) and amiloride (500 microM). Exposure to 50 microM-cadmium left a fraction of the T-type current intact but blocked N- and L-type current. This T-like component needed extremely negative holding potentials to be completely reprimed. 4. Whole-cell N-type Ca2+ channel current was blocked by omega-conotoxin (1 microM). From a holding potential of -90 mV, omega-conotoxin decreased the peak whole-cell current by 33%. 5. A slowly inactivating high-threshold Ca2+ current (L-type) that was present at depolarized holding potentials, displayed dihydropyridine sensitivity. From a holding potential of -50 mV, addition of the dihydropyridine Ca2+ channel antagonist nimodipine (2 microM) to the bath decreased whole-cell peak current by 45%. Interestingly, at negative holding potentials nimodipine worked as an agonist. From a holding potential of -90 mV, nimodipine (2 microM) increased peak current at test potentials from -50 to -20 mV and shifted the peak of the current-voltage relationship in the hyperpolarizing direction similar to the effect of Ca2+ channel agonist Bay K 8644. Exposure to Bay K 8644 (2 microM) increased peak current and single channel open probability independent of holding potential while shifting the peak of the whole-cell current-voltage relationship 11 mV in the hyperpolarizing direction. Our experiments suggest that there are approximately the same number of L-type as omega-conotoxin sensitive N-type Ca2+ channels in CA3 neurones. 6. A high-voltage-activated whole-cell current was still present in cells exposed to both nimodipine and omega-conotoxin (2 and 1 microM, respectively) suggesting the existence of a fourth type of Ca2+ channel in these neurones or that a population of either L-type or N-type Ca2+ channels did not respond to dihydropyridine antagonists or omega-conotoxin, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008978 Mollusk Venoms Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine. Conus Venoms,Octopus Venoms,Snail Venoms,Conus Venom,Mollusc Venoms,Mollusk Venom,Octopus Venom,Snail Venom,Venom, Conus,Venom, Mollusk,Venom, Octopus,Venom, Snail,Venoms, Conus,Venoms, Mollusc,Venoms, Mollusk,Venoms, Octopus,Venoms, Snail
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009532 Nickel A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.
D009553 Nimodipine A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. Admon,Bay e 9736,Brainal,Calnit,Kenesil,Modus,Nimodipin Hexal,Nimodipin-ISIS,Nimodipino Bayvit,Nimotop,Nymalize,Remontal,Bayvit, Nimodipino,Hexal, Nimodipin,Nimodipin ISIS,e 9736, Bay
D002104 Cadmium An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.
D004095 Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
D004553 Electric Conductivity The ability of a substrate to allow the passage of ELECTRONS. Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea

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