Neuroscience Letters, 89 (1988) 161 164 161 Elsevier Scientific Publishers Ireland Ltd. NSL 05393 The mode of action of guanidine on mouse motor nerve terminals Jordi Molg6 and Alberto Mallart Unit~; de Physiologic Neuromusculaire, Laboratoire de Neurobiologie Cellulaire et Molt;culaire, C.N.R.S. 91190, Gif sur Yvette (France) (Received 19 February 1988: Accepted 10 March 1988) Key words: Guanidinc: Motor nerve terminal: Presynaptic current: Potassium channel: Neurotransmitter release; Mouse The action of guanidine on presynaptic membrane currents has been investigated to elucidate its facilita- tory effect on phasic transmitter release at the mouse neuromuscular juntion. Guanidine (2 10 mM) pro- duced a near complete inhibition of the fast voltage-dependent K current. This effect is expected to allow an increase in Ca z' influx and, thereby, in transmitter release upon nerve stimulation. Guanidine failed to block the Ca-dependent K current of the nerve terminals. Guanidine has long been known for its ability to enhance the phasic evoked release of acetylcholine at the neuromuscular junction of skeletal muscle [7, 9, 14, 15]. The drug has been shown to increase muscle strength concomitant with electromyo- graphic improvement in patients with the myasthenic syndrome of Eaton-Lambert [4] and to antagonize the neuromuscular block produced by botulinum A toxin in experimental animals [11]. The action of guanidine is not restricted to cholinergic ter- minals since the drug also enhances noradrenaline release from sympathetic nerve endings [8]. The mode of action of guanidine in increasing transmitter release has been related to a direct action of the drug on voltage-sensitive calcium channels of the nerve terminal, in such a way that the entry of Ca 2 + is facilitated [10]. Alternati- vely, the drug could bind to fixed negative charges on the external surface of the pre- synaptic membrane causing a shift in the negative direction of the voltage dependen- cy of Ca channel opening [14]. Finally, since guanidine produces a widening of the intracellularly recorded action potential in the caliciform presynaptic terminals of the chick ciliary ganglion [2], one cannot exclude an action of this drug on the K conduc- tance of the presynaptic membrane. In the present study we have used the technique of presynaptic current recording Correspondence: A. Mallart, Unit6 de Physiologic Neuromusculaire, Laboratoire de Neurobiologie Cellu- laire et Mol6culaire, C.N.R.S. 91190, Gif sur Yvene, France. 0304-3940,'88/$ 03.50 (~ 1988 Elsevier Scientific Publishers Ireland Ltd.