Opposing effects of phorbol esters on transmitter release and calcium currents at frog motor nerve endings

The Journal of Physiology
R S RedmanEugene M Silinsky

Abstract

1. Phorbol esters activate protein kinase C (PKC) and also increase the secretion of neurotransmitter substances by an unknown mechanism. To evaluate whether the stimulatory effects of such agents on acetylcholine (ACh) secretion occur as a consequence of stimulation of Ca2+ entry, we made electrophysiological measurements of ACh secretion (i.e. endplate potentials, EPPs) and the component of the prejunctional perineural voltage change associated with nerve terminal calcium currents (perineural calcium current) at frog neuromuscular junctions. 2. In the first series of experiments, modest concentrations of K+ channel blockers were employed so that simultaneous measurements of EPP amplitudes and perineural calcium currents could be made. In these experiments, 12-O-tetradecanoylphorbol 13-acetate (TPA; 162 nM) and phorbol 12,13-dibutyrate (PDBu; 100-200 nM) each increased ACh release but simultaneously decreased the calcium component of the prejunctional perineural current TPA and PDBu also inhibited perineural calcium currents in the presence of higher concentrations of K+ channel blockers. 3. Blockade of Ca2+ channels by Cd2+ prevented the action of PKC stimulators on perineural waveforms. 4. The inactive compound 4-alpha-phorb...Continue Reading

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Citations

Jun 24, 2000·Biochimie·R R DuncanR H Chow
Jul 22, 1998·Progress in Neurobiology·H Majewski, L Iannazzo
Jun 14, 2000·Current Opinion in Neurobiology·N BroseJ Rettig
Jul 12, 2002·British Journal of Pharmacology·Michael FährmannUrsula Seidler
Nov 6, 2009·Journal of Neurophysiology·Chun Yun Chang, Steven Mennerick
Apr 4, 2008·Journal of Neurophysiology·Timothy J Searl, Eugene M Silinsky
Apr 7, 2004·British Journal of Pharmacology·Silvana De LorenzoAdriana Losavio
Apr 25, 2003·British Journal of Pharmacology·Eugene M Silinsky, Timothy J Searl
Sep 3, 2004·Brain Research Bulletin·R RamakrishnanN Suthanthirarajan
Mar 2, 2005·Biochemical and Biophysical Research Communications·Nobuaki OzakiYutaka Oiso
Dec 15, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ana P SilvaJoão O Malva
Sep 6, 2003·The European Journal of Neuroscience·E SokolovaR Giniatullin
Jan 12, 2001·Journal of Neurophysiology·J K Angleson, W J Betz

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