Involvement of L-type calcium channels and mitochondria in post-tetanic potentiation: Is it a general rule for different types of synapses?

Abstract

Our experiments and studies of a few other authors demonstrated that L-type calcium channels and mitochondria are involved in the induction of post-tetanic potentiation (PTP) in a number of preparations (Aplysia central nervous system, hippocampal cell cultures, crayfish neuromuscular junctions, etc.). We extend this conclusion on cortical synapses by the demonstration that inhibitors of mitochondrial Ca 2+ uptake and release suppress PTP in rat neocortical cell cultures.Post-tetanic potentiation (PTP) is a form of shortterm enhancement of the synaptic efficacy induced by trains of repetitive action potentials (APs) in a presynaptic neuron. It is generally accepted that PTP results from the effects of residual elevation in the presynaptic [Ca 2+ ] i , influencing one or more specific molecular targets distinct from secretory triggers responsible for the phasic release of transmitter to single (more correctly, low-frequency) APs [1]. Here, we hypothesize that the involvement of L-type calcium channels and mitochondria in the induction of PTP could be another general mechanism for this form of plasticity.We believe that we were the first who obtained direct pharmacological evidence indicating the involvement of L-type calcium channels in PTP [2]. Namely, we demonstrated that PTP in Aplysia central excitatory synapses is dramatically decreased in the presence of dihydropyridines (nifedipine, darodipine, or isradipine). It should be noted that despite a clearly pronounced effect of dihydropyridines on PTP, control (pretetanic) postsynaptic potentials were not affected in the presence of these drugs. These results showed that L-type calcium channels are not involved in synaptic transmission per se.More recently, rather similar observations were reported regarding mammalian central inhibitory (GABA-ergic) synapses in a few preparations [3][4][5]. In particular, it was shown that both nifedipine [3,5] and isradipine [3] significantly reduced PTP in hippocampal cell cultures with no effect on synaptic potentials evoked by low-frequency stimulation.The involvement of mitochondria in the induction of PTP was first demonstrated by Tang and Zucker [6] in crayfish neuromuscular junctions. Indeed, several inhibitors of mitochondrial Ca 2+ uptake and release, namely tetraphenylphosphonium (TPP+), carbonyl cyanide m-chlorophenylhydrazone (CCCP), and ruthenium red, blocked PTP and the persistence of presynaptic residual [Ca 2+ ] i , while inhibitors of the endoplasmic reticulum Ca 2+ pump and activators of the release channels, such as thapsigargin, 2,5-di-(tert-butyl)-1,4-benzohydroquinone, and caffeine, demonstrated no effect [6]. It was concluded that PTP results from a slow efflux of tetanically accumulated