AJP - Regulatory, Integrative and Comparative Physiology, Vol 259, Issue 3 427-R438, Copyright © 1990 by American Physiological Society
Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats
S. Shapira, O. M. Adeyemo and G. Feuerstein
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
omega-Conotoxin (omega-ctx) was used as a probe for studying the putative
role of brain L/N-type Ca2+ channels in regulation of autonomic functions.
Rats were injected intracerebroventricularly (icv) with omega-ctx, and
hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx
(0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior,
complex thermoregulatory changes, and motor deficits lasting up to 48 h.
Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P
less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less
than 0.05) associated with increased circulating levels of norepinephrine
and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory
shock and death. Central administration of 3,4,5-trimethoxybenzoic acid
8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg),
neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100
nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type
Ca2(+)-channel blockers, respectively, did not cause any behavioral or
hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg
icv) caused a mild transient pressor response. Pretreatment with the
gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined
intravenous pretreatment with propranolol and N-methylatropine blocked the
omega-ctx effects. Our data suggest that omega-ctx actions in the brain
involve central GABAergic mechanisms modulated by yet a different type of
Ca2+ channels not characterized by any of the known voltage-operated Ca2+
channels.
