Do potassium ions released from nerve modulate the sensitivity to transmitter in ‘close’ neuro-effector junctions of the vas deferens?

Abstract

In guinea-pig isolated vas deferens, in which the neural stores of noradrenaline had been labelled by preincubation with [ 3H](−)-noradrenaline, the secretion of tracer noradrenaline induced by electrical stimulation of the extramural nerves with trains of 300 shocks at 10 Hz was markedly depressed when the K + concentration of the medium was raised stepwise from 2.7 mM. Although at 21.6 m m K + the secretion of noradrenaline was reduced to less than 25% of the control level, the strength of the early twitch contraction in response to the same stimulation was almost doubled. Thus, noradrenaline could be the transmitter for the twitch only if the rise in [K +] in the medium had increased the responsiveness of the twitch generating mechanism to noradrenaline by about 10-fold. This turned out to be the case. Cumulative addition of noradrenaline to the bathing medium caused a rise in basal tone and, superimposed on this, twitch-like contractions of the vas. The threshold for the twitches was drastically lowered as [K +] in the medium was raised, while their strength increased. An eight-fold rise in [K +] caused the responsiveness of the twitch generating mechanism to noradrenaline to increase fifty-fold. These findings could be of physiological relevance if a rise in [K +] restricted to the cleft of neuro-effector junctions similarly lowers the threshold of the postjunctional membrane to the neurotransmitter secreted from the prejunctional terminals. In tissues where the transmitter does not primarily promote K + efflux from the postjunctional cells, the additional K + would initially have to be derived from nerve. Judging from evidence in the literature concerning K + release from mammalian C-fibres, activation of the motor nerves to the close junctions in the vas deferens may well result in a local and transient rise in [K +] to levels sufficient to cause considerable focal depolarization of the subsynaptic part of the muscle membrane, and thus possibly to facilitate neuro-effector transmission. The sensitizing effect of high [K +] in the medium was not restricted to noradrenaline but could be demonstrated for acetylcholine as well; this suggests that variation in the local concentration of K + may possibly exert similar modulating effects in other close junctions, regulating the sensitivity of the postjunctional membrane to the transmitter specific for the individual junction.