Neomycin inhibits K+-induced force and Ca2+ channel current in rat arterial smooth muscle.
The techniques of small vessel isometric myography and patch clamp were used to investigate the action of neomycin on K+-induced isometric force and voltage-gated Ca2+ channel currents in rat arterial smooth muscle. Neomycin and the dihydropyridine (DHP) Ca2+ channel antagonist (-)202-791 concentration-dependently and reversibly inhibited 40 mM K+-induced isometric force in rings of rat mesenteric and basilar arteries (IC50 values of 70 microM and 1. 2 nM, respectively, n = 10 and 4). Elevation of [Ca2+]o by a factor of 2 significantly reduced the IC50 values for inhibition of K+-induced force for both neomycin and (-)202-791 (192 microM and 3. 7 nM, respectively, n = 6 and 4), but did not affect the Hill coefficient of the concentration/effect relationships. In patch-clamp experiments using freshly isolated basilar arterial myocytes, the voltage-gated inward current carried by Ba2+ was reversibly and concentration-dependently inhibited by neomycin (IC50 32 microM, n = 3). The concentration/effect curve for inhibition of the inward Ba2+ current by neomycin was significantly shifted to the right when [Ba2+]o was raised from 1.8 mM to 10 mM (IC50 144 microM, n = 8). Our findings suggest that neomycin relaxes high-K+-induced force in rat isolated mesenteric and basilar arteries largely by inhibition of voltage-dependent and DHP-sensitive Ca2+ channels.
Langton
P D
PD
Department of Physiology, School of Medical Sciences, University Walk, University of Bristol, UK-Bristol BS8 1TD, United Kingdom.
Farley
R
R
Everitt
D E
DE
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001464:Barium / Q000494:pharmacology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D015640:Ion Channel Gating; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009355:Neomycin / Q000494:pharmacology*; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D004095:Dihydropyridines; D001464:Barium; D009355:Neomycin; D011188:Potassium; D002118:Calcium