Membrane potential responses of the mouse anococcygeus muscle to ionophoretically applied noradrenaline

Abstract

1. Membrane potential responses to ionophoretically applied noradrenaline and to field stimulation were studied in the mouse anococcygeus muscle using intracellular recording techniques.2. The ionophoretic application of noradrenaline produced charge-dependent depolarizations whose total duration was 1-2 s at room temperature and which were characterized by a delay between the start of the ionophoretic pulse and the onset of depolarization (termed the latency of the responses). On occasion ionophoresis of noradrenaline did not depolarize the muscle even though it seemed that successful ejection of noradrenaline had occurred as small localized contractions could be seen.3. The characteristics of these depolarizations were unaffected by tetrodotoxin (10(-7) M) and could not be reproduced when the ionophoretic pipette contained 2 M-NaCl rather than noradrenaline. Moreover noradrenaline still produced depolarizations in denervated muscle and thus it is concluded that the responses were caused by noradrenaline released from the ionophoretic micropipette and not from the intrinsic noradrenergic nerves.4. Field stimulation of innervated muscle usually evoked excitatory junction potentials (e.j.p.s), but sometimes inhibitory junction potentials (i.j.p.s) or a mixture of e.j.p.s and i.j.p.s were observed. The time course of the e.j.p.s was slightly longer than that of the ionophoretic depolarizations which was accounted for by a smaller latency of the ionophoretically induced responses.5. The pharmacology of the nerve-evoked e.j.p.s and the ionophoretically induced depolarizations was similar as both types of responses were antagonized by alpha(1)-adrenoceptor blocking agents (phentolamine and prazosin) but were unaffected by the beta-adrenoceptor antagonist, propranolol. It is probable that noradrenaline released from the intrinsic nerves and that from the ionophoretic micropipette were acting on the same adrenoceptors.6. The latency and to a lesser extent the rise-time of the depolarizations produced by the ionophoretic application of noradrenaline was highly sensitive to changes in temperature of the bathing fluid (Q(10)s > 2) whereas the half-decay time was relatively insensitive to temperature changes (Q(10) approximately 1.5). In addition the latency of the depolarizations was not altered by inhibiting the noradrenaline-uptake mechanism with cocaine (2 x 10(-6) M) or by alpha-adrenoceptor blocking agents. Thus it seems likely that the latency of the responses is a property of the noradrenaline-receptor interaction rather than being caused by other phenomena such as diffusion of noradrenaline.