title: The mechanisms of multi-component paired-pulse facilitation of neurotransmitter release at the frog neuromuscular junction.
abstract: We have studied the mechanisms of paired-pulse facilitation (PPF) of neurotransmitter release in isolated nerve-muscle preparations of the frog cutaneous pectoris muscle. In normal extracellular Ca(2+) concentration ([Ca(2+)](o), 1.8 mM), as the interpulse interval was increased from 5 to 500 ms, PPF decayed as a sum of two exponential components: a larger but shorter first component (F1) and a smaller but more prolonged second component (F2). In low [Ca(2+)](o) (0.5 mM), both F1 and F2 increased, and a third "early" component (Fe) appeared whose amplitude was larger and whose duration was shorter than F1 or F2. In the presence of the "fast" Ca(2+) buffer BAPTA-AM, Fe disappeared, whereas F1 and F2 decreased in amplitude and duration. In contrast, the "slow" Ca(2+) buffer EGTA-AM caused a decrease of Fe and reduction or complete blockade of F2, without any changes of F1. In solutions containing Sr(2+) (1 mM), the magnitude of Fe was decreased, F1 was significantly reduced and shortened, but F2 was unaffected. Application of the calmodulin inhibitor W-7 (10 microM) at normal [Ca(2+)](o) produced a marked decrease of F2, and at low [Ca(2+)](o), a complete blockade of Fe. These results suggest that PPF at frog motor nerve terminals is mediated by several specific for different PPF components intraterminal Ca(2+) binding sites, which trigger neurotransmitter release. These sites have a higher affinity for Ca(2+) ions and are located farther from the release-controlling Ca(2+) channels than the Ca (2+) sensor that mediates phasic release.
authors.affiliation: Department of Physiology, Kazan State Medical University, Kazan, Russia. maratm80@list.ru
authors.forename: Marat A
authors.initials: MA
authors.lastname: Mukhamedyarov
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Grishin
authors.forename: Andrey L
authors.initials: AL
authors.lastname: Zefirov
authors.forename: András
authors.initials: A
authors.lastname: Palotás
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods*; D017774:Long-Term Potentiation / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D011895:Rana ridibunda / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents