Phorbol ester enhances synaptic transmission at crustacean neuromuscular junctions.
Effects of phorbol ester (PE) (4 beta-phorbol-12,13-dibutyrate) on transmitter release were studied in the deep extensor neuromuscular system of the prawn, Macrobrachium rosenbergii. Our findings show that PE enhances transmitter release as indicated by an increase in the quantal content. PE had no post-synaptic effects. The increase in release is accompanied by a slight decline in twin pulse facilitation, suggesting a minor increase in Ca2+ entry. The fact that the increase in Ca2+ entry has a minor contribution to the PE effect is supported by the following observations: the duration of facilitation was not affected by PE, and 3,4-diaminopyridine (3,4-DAP), which by itself increased release, did not reduce the effect of PE. The time course of release was measured from synaptic delay histograms, upon which PE had no effect. This finding indicates that protein kinase C (PKC) is probably not involved in the rate limiting step of the process of secretion. The log/log plot of the initial part of the delay histogram is not affected by PE, suggesting a lack of effect on cooperativity of the release process. Increased release by loading the presynaptic terminal with Ca2+ either by pretreatment with Ca2+ ionophore or by frequent stimulation prevented further increase in release by PE. We conclude that the main effect of PE is confined to stages of release that are secondary to the first elevation in presynaptic Ca2+. PKC in this system probably plays a role in long term modulation of release, and it can be activated in processes leading to presynaptic Ca2+ accumulation.
Gilat
E
E
Otto Loewi Center for Cellular and Molecular Neurobiology, Department of Neurobiology, Hebrew University of Jerusalem, Israel.
Hochner
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D033364:Decapoda; D008564:Membrane Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D015240:Phorbol 12,13-Dibutyrate; D002118:Calcium