NEOMYCIN INHIBITS K-INDUCED FORCE AND CA2+ CHANNEL CURRENT IN RAT ARTERIAL SMOOTH-MUSCLE()

The techniques of small vessel isometric myography and patch clamp wer e used to investigate the action of neomycin on K+-induced isometric f orce and voltage-gated Ca2+ channel currents in rat arterial smooth mu scle. 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 arterie s (IC50 values of 70 mu M and 1.2 nM, respectively, n = 10 and 4). Ele vation of [Ca2+](o) by a factor of 2 significantly reduced the IC50 va lues for inhibition of K+-induced force for both neomycin and (-)202-7 91 (192 mu M and 3.7 nM, respectively, n = 6 and 4), but did not affec t the Hill coefficient of the concentration/effect relationships. In p atch-clamp experiments using freshly isolated basilar arterial myocyte s, the voltage-gated inward current carried by Ba2+ was reversibly and concentration-dependently inhibited by neomycin (IC50 32 mu M, n = 3) . The concentration/effect curve for inhibition of the inward Ba2+ cur rent by neomycin was significantly shifted to the right when [Ba2+](o) was raised from 1.8 mM to 10 mM (IC50 144 mu M, n = 8). Our findings suggest that neomycin relaxes high-K+-induced force in rat isolated me senteric and basilar arteries largely by inhibition of voltage-depende nt and DHP-sensitive Ca2+ channels.