Enhancement of a slow potassium current component by uranyl nitrate and its relation to the antagonism on β-bungarotoxin in the mouse motor nerve terminal

Uranyl nitrate (UO 2(NO 3) 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 UO 2 2+ induced an initial twitch depression followed by a later twitch potentiation in low (0.35 mM) Ca 2+ medium. Although UO 2 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 UO 2 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 β-bungarotoxin, which has been shown to be capable of blocking the K +-current of the motor nerve terminal, it was proposed that UO 2 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 Ca 2+ and Cd 2+ but attenuated by high K + and high Ca 2+. These cation effects not only supported UO 2 2+-induced IK (s) current but also excluded the possibility of an enhancement of Ca 2+-activated K +-current induced by UO 2 2+ plus TEA. The significance of this enhancement of IK (s) induced by UO 2 2+ has been elucidated by the finding that dendrotoxin inhibited but tetraethylammonium potentiated not only UC 2 2+-induced IK (s) but also UO 2 2+-induced twitch depression. Therefore, it is concluded that in addition to the blockade of IK (f), UO 2 2+ can also enhance IK (s)-like current which accounts for presynaptic inhibition of the twitch contractions. Moreover, UO 2(NO 3) 2 has been found to be a selective potent antagonist of β-bungarotoxin (β-BuTX) in blocking the neuromuscular transmission of mouse phrenic nerve diaphragm. In accordance with their effects on UO 2 2+-induced IK (s), TEA markedly potentiated UO 2 2+ in antagonizing the neuromuscular blocking action of β-BuTX, while 4-AP, DTX, high K + and Ca 2+ all reversed the antagonistic action of UO 2 2+ plus TEA against β-BuTX. These findings provide more evidence that IK (s) plays a role in the regulation of transmitter release and UO 2 2+ antagonizes the neuromuscular blocking action of β-BuTX through their interaction at least in part on