Interactions between the effects of yohimbine, clonidine and [Ca]o on the electrical response of the mouse vas deferens.

Excitatory junction potentials (e.j.ps) were recorded from mouse vas deferens and resolved into families of 'discrete events' (d.es) reflecting intermittent release of packets of transmitter from one or a few sites. Within families d.es vary in amplitude between a few preferred values unaffected by any treatments used in these experiments. As [Ca]o is raised from 1.1 to 4.0 mM there is a rise in d.e. amplitude due to an increase in the frequency of large events and a decrease in that of small. At all [Ca]o clonidine reduces d.e. amplitude by increasing failures and small events and decreasing large events. Yohimbine has opposite effects. Both drug effects are concentration-dependent in the range 5 X 10(-9) - 10(-6)M. As [Ca]o is raised from 1.1 to 4.0 mM, and therefore more natural agonist is released, clonidine becomes more effective at altering d.e. amplitude whereas yohimbine becomes less so. With very low frequency stimulation yohimbine elevates e.j.p. amplitude only if [Ca]o is below 1.6 mM. These results are not easily compatible with the notion that yohimbine breaks a 'negative feedback' control of transmitter release.