Enhancement of a slow potassium current component by uranyl nitrate and its relation to the antagonism on beta-bungarotoxin in the mouse motor nerve terminal.
Uranyl nitrate (UO2(NO3)2) has been shown to be capable of increasing transmitter release from the motor nerve accompanied by the potentiation of nerve evoked muscle contraction. In this paper, we have demonstrated that UO2(2+) induced an initial twitch depression followed by a later twitch potentiation in low (0.35 mM) Ca2+ medium. Although UO2(2+) has been identified as a K(+)-channel blocker, we have found it only partially blocked the fast K(+)-current (IK(f) as recorded in the perineurial sheath of the mouse triangularis sterni preparation. Increasing the concentration of UO2(2+) to a high concentration of 0.4 mM did not further inhibit IK(f) but markedly prolonged the duration of the outward current of the nerve terminals. From the time course of its appearance together with the specific inhibition by 4-aminopyridine, dendrotoxin and beta-bungarotoxin, which has been shown to be capable of blocking the K(+)-current of the motor nerve terminal, it was proposed that UO2(2+) prolonged the duration of the nerve terminal spikes by an enhancement of an IK(s)-like current, which was further characterized by its susceptibility to be enhanced by low K+, low Ca2+ and Cd2+ but attenuated by high K+ and high Ca2+. These cation effects not only supported UO2(2+)-induced IK(s) current but also excluded the possibility of an enhancement of Ca(2+)-activated K(+)-current induced by UO2(2+) plus TEA. The significance of this enhancement of IK(s) induced by UO2(2+) has been elucidated by the finding that dendrotoxin inhibited but tetraethylammonium potentiated not only UO2(2+)-induced IK(s) but also UO2(2+)-induced twitch depression.(ABSTRACT TRUNCATED AT 250 WORDS)
Chao
K F
KF
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Lin-Shiau
S Y
SY
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009046:Motor Neurons / Q000187:drug effects*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013997:Time Factors; D014502:Uranyl Nitrate / Q000494:pharmacology*
D002038:Bungarotoxins; D004546:Elapid Venoms; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D014502:Uranyl Nitrate; D019789:Tetraethylammonium; C020273:dendrotoxin; D002118:Calcium