Effects of modulating Ca²⁺ entry and activating prejunctional receptors on facilitation of excitatory junction potentials in the guinea-pig vas deferens in vitro

Abstract.

This study investigated the effects of changing the extracellular Ca²⁺ concentration on facilitation of excitatory junction potential (EJP) amplitude during trains of 20 stimuli at 1 Hz at sympathetic neuroeffector junctions in the guinea-pig vas deferens. These effects were compared with those of Ca²⁺ channel blockers and agents which act at prejunctional receptors to increase or decrease neurotransmitter release. In these experiments, α-adrenoceptor-mediated autoinhibition of neurotransmitter release was blocked by the α-adrenoceptor antagonist, phentolamine (1 µM).

Varying the extracellular Ca²⁺ concentration (0.75–6 mM) changed the amplitude of EJPs without affecting the maximum level of facilitation during the trains of stimuli. Reductions in Ca²⁺ concentration (from 2 mM) were associated with a slowing in the rate of development of facilitation. The Ca²⁺ channel antagonists, Cd²⁺ (2 µM and 5 µM) and ω-conotoxin GVIA (10 nM), and agents which act at prejunctional receptors to reduce neurotransmitter release, adenosine (100 µM and 1000 µM) and prostaglandin E₂ (PGE₂; 0.1 nM and 1 nM), produced similar effects to those of lowering the extracellular Ca²⁺ concentration. Raising the extracellular Ca²⁺ concentration (from 2 mM) increased the rate of development of facilitation. Angiotensin II (AII; 0.5 µM) produced similar effects to raising extracellular Ca²⁺. However, isoprenaline (1 µM), while increasing EJP amplitude, reduced the maximum level of facilitation and was without effect on the rate of development of facilitation.

In the guinea-pig vas deferens EJPs are produced by neurally released ATP. Thus, the findings support the idea that adenosine, PGE₂ and AII change ATP release by modifying Ca²⁺ entry into the nerve terminal. However, the effects of isoprenaline may not solely be accounted for by modifications in Ca²⁺ entry.