ISSN:
1432-2013
Keywords:
Sensory neurons
;
Motoneurons
;
Voltage-gated calcium current
;
ω-Conotoxin GVIA
;
ω-Agatoxin IVA
;
Nimodipine
;
Verapamil
;
Diltiazem
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract We compared the effects of representative members of three major classes of cardiac L-type channel antagonists, i.e. dihydropyridines (DHPs), phenylalkylamines (PAAs) and benzothiazepines (BTZs) on high-voltage-activated (HVA) Ca2+ channel currents recorded from a holding potential of −100 mV in rat ventricular cells, mouse sensory neurons and rat motoneurons. Nimodipine (DHP), verapamil (PAA) and diltiazem (BTZ) block the cardiac L-type Ca2+ channel current (EC50: 1 μM, 4 μM and 40 μM, respectively). At these concentrations, the drugs could also inhibit HVA Ca2+ channel currents in both sensory and motor neurons. Large blocking effects (〉 50%) could be observed at 2–10 times these concentrations. The ω-conotoxin-GVIA-sensitive (ω-CTx-GVIA, N-type), ω-agatoxin-IVA-sensitive (ω-Aga-IVA, P- and Q-types) and non-L-type ω-CTx-GVIA-, ω-Aga-IVA-insensitive (R-types) currents accounted for more than 90% of the global current. Furthermore, our data showed that ωCTx-GVIA and ω-Aga-IVA spare L-type currents and have only additive blocking effects on neuronal HVA currents. We conclude that DHPs, PAAs and BTZs have substantial inhibitory effects on neuronal non-L-type Ca2+ channels. Inhibitions occur at concentrations that are not maximally active on cardiac L-type Ca2+ channels.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00374372
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