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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kleinhaus, A. L. Taft, W. C. Yang, J. Delorenzo, R. J. Johansen, J. |
| Abstract | Benzodiazepines (BZs) in micromolar concentrations inhibit Mn2+- and Co2+-sensitive regenerative divalent cation potentials, which are revealed in the presence of tetraethylammonium ion, in leech nociceptive neurons (N cells). This BZ effect is reversible and dose-dependent. The BZs, like Mn2+ and Co2+, inhibit the maximum rate of depolarization (Vmax) and duration of divalent cation potentials at concentrations that do not significantly affect resting membrane potential or Vmax of the Na+-dependent action potential. Ultraviolet-induced BZ binding to micromolar-affinity sites in ganglia and isolated cells irreversibly blocks Ca2+ conductance in neurons without significantly affecting resting membrane potentials. BZ binding studies with leech neuronal membrane show saturable, specific binding in the micromolar concentration range that was similar to BZ binding to synaptosomal membrane fractions. The apparent Kd obtained from the micromolar-affinity BZ binding curve for leech ganglionic membrane preparations agrees well with the apparent Ki estimated from the dose-response curve measuring BZ inhibition of Vmax of the divalent cation potentials. These findings indicate that BZs act like Ca2+-channel antagonists in intact neuronal preparations and are consistent with the hypothesis that BZ binding to micromolar-affinity receptors modulates voltage-gated Ca2+ channels. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 11 |
| Volume Number | 82 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1985-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Benzodiazepines Pharmacology Calcium Physiology Neurons Drug Effects Action Potentials Animals Cobalt Dose-Response Relationship, Drug Electric Conductivity Electrophysiology Ganglia Metabolism Radiation Effects Kinetics Leeches Manganese Sodium Strontium Ultraviolet Rays Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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