Inhibition of Ca2+ conductance in identified leech neurons by benzodiazepines.

Abstract

Benzodiazepines (BZs) in micromolar concentrations inhibit (12). The intracellular recording techniques used in this study have been described in detail (6, 12). To facilitate equilibration of the drugs, the connective capsules overlaying ganglia were removed. Divalent cation potentials were elicited in Na'-free Et4N+/Ringer's solution (1-3 mM SrCl2 or CaCl2/4 mM KCl/25 mM Et4NCl/220 mM sucrose/10 mM glucose/10 mM Tris C1, pH 7.4) after cell identification in normal Ringer's solution. Permanent recording was done with a PDP-8 computer system which digitized the traces at 23 kHz. The maximum rates of depolarization (V,) of the Na+-dependent action potentials of N cells were analyzed by a computer subroutine written for this purpose (14,15). The Vis of the divalent cation potentials were determined by differentiation of the action potential with an analog circuit having a time constant of 1 msec. Due to the low solubility of BZs in aqueous media, stock solutions of these drugs were made in absolute ethanol and then diluted to final concentration in Na+-free Et4N+/Ringer's solution. The 3935The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Commitment to differentiation of murine erythroleukemia cells involves a modulated plasma membrane depolarization through Ca2+‐activated K+ channels

“…51, suggests the so far unexplored possibility that benzodiazepines antagonize the inactivation of the Ca2+-sensitive channels. This hypothesis, however, is difficult to reconcile with the recent report that benzodiazepines act as Ca2+ antagonists (Johansen et al, 1985).…”

The triakontatetraneuropeptide TTN increases [Ca2+]i in rat astrocytes through activation of peripheral‐type benzodiazepine receptors

“…In addition, peripheral-type BZ have been reported to increase calcium influx in astroglial cells (Zhao et al, 1996) and to reduce cytosolic calcium concentration ([Ca 2ϩ ] i ) in rat pheochromocytoma cells (Nakazawa et al, 1991), bovine adrenal glomerulosa cells (Python et al, 1993), and leech neurons (Johansen et al, 1985). Recently, we have also found that TTN activates voltage-operated calcium channels in frog adrenocortical cells (Lesouhaitier et al, 2000).…”

Benzodiazepine Receptors and Their Relationship to the Treatment of Epilepsy

“…The uptake of 45Ca into synaptosomes is blocked by micromolar concentrations of benzodiazepine and by phenytoin; this has been shown to be a specific effect on the voltage-dependent Ca++ entry (Taft and DeLorenzo, 1984;Johansen et al, 1985). Various benzodiazepines show similar relative potency for inhibiting micromolar diazepam binding, synaptosomal Ca++ uptake, and suppression of maximal electroshock.…”

“…The low affinity benzodiazepine binding sites, originally described by Bowling and DeLorenzo (1982), are thought to operate on presynaptic terminals to reduce Ca++ entry and, thus, synaptic neurotransmitter release. The uptake of 45Ca into synaptosomes is blocked by micromolar concentrations of benzodiazepine and by phenytoin; this has been shown to be a specific effect on the voltage-dependent Ca++ entry (Taft and DeLorenzo, 1984;Johansen et al, 1985). Various benzodiazepines show similar relative potency for inhibiting micromolar diazepam binding, synaptosomal Ca++ uptake, and suppression of maximal electroshock.…”