Inhibition of Ca2+ conductance in identified leech neurons by benzodiazepines.
AUTOR(ES)
Johansen, J
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=397904Documentos Relacionados
- Ca2+ -activated K+ conductance in internally perfused snail neurons is enhanced by protein phosphorylation.
- Inhibition of Ca2+ entry by Ca2+ overloading of intracellular Ca2+ stores in human platelets.
- Nitric oxide donors enhanced Ca2+ currents and blocked noradrenaline-induced Ca2+ current inhibition in rat sympathetic neurons.
- Ca2+ dynamics in the lumen of the endoplasmic reticulum in sensory neurons: direct visualization of Ca2+-induced Ca2+ release triggered by physiological Ca2+ entry
- Inactivation of single Ca2+ channels in rat sensory neurons by extracellular Ca2+.