Neomycin inhibits K+-induced force and Ca2+ channel current in rat arterial smooth muscle.

ABSTRACT

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.