Ryanodine produces a low frequency stimulation‐induced NMDA receptor‐independent long‐term potentiation in the rat dentate gyrus in vitro.

Abstract

1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+ channels which regulate Ca2+ release from intracellular Ca2+ stores. 2. In control media, high frequency stimulation (HFS) induced LTP, and prolonged low frequency stimulation (LFS) induced long-term depression (LTD), of field excitatory postsynaptic potentials (EPSPs) and patch clamped excitatory postsynaptic currents (EPSCs).3. In the presence of ryanodine, at a threshold concentration of about 1 uM, HFS-induced LTP was inhibited, whereas LFS (5 Hz, 900 pulses) now induced LTP.

Release and sequestration of calcium by ryanodine‐sensitive stores in rat hippocampal neurones

“…Role of ryanodine-sensitive Ca¥ stores in CICR Contrasting the view that neuronal ryanodine-sensitive Ca¥ stores are essentially buffers of cytosolic Ca¥, is the view that these stores participate in the boosting of incoming Ca¥ signals via a CICR mechanism (Hua et al 1993;Llano et al 1994;Shmigol, Verkhratsky and Isenberg, 1995;Kano et al 1995), and thus may have a crucial role in neuronal plasticity (Schiegg et al 1995;Reyes & Stanton, 1996;Wang et al 1996) and excitotoxicity (see Mody & MacDonald, 1995). This view contends that, like in cardiac muscle (Nabauer et al 1989), cytosolic Ca¥ acts as a RyR agonist to discharge Ca¥ from the stores.…”

“…Accordingly, tetanic synaptic stimulation of CA1 pyramidal cells in a slice preparation reportedly induced Ca¥ release from dendritic ryanodine-sensitive Ca¥ stores (Alford, Frenguelli, Schofield & Collingridge, 1993). A RyR-mediated CICR process, preferentially localized to dendritic spines, may boost the magnitude and duration of the Ca¥ signals required for induction of long-term potentiation of synaptic efficacy in the hippocampus (Schiegg, Gerstner, Ritz & van Hemmen, 1995;Wang, Wu, Rowan & Anwyl, 1996). However, ryanodine-sensitive Ca¥ stores in different types of cultured rat central neurones (including CA1 hippocampal neurones) were reported to be empty at rest and to accumulate Ca¥ only after its entry via voltagegated Ca¥ channels in the plasmalemma (Brorson, Bleakman, Gibbons & Miller, 1991;Shmigol, Kirischuk, Kostyuk & Verkhratsky, 1994).…”

Diacylglycerol kinase ɛ regulates seizure susceptibility and long-term potentiation through arachidonoyl– inositol lipid signaling

“…Excitatory postsynaptic potentials (EPSPs) in response to stimulation of the perforant path were recorded at a frequency of 0.05 Hz and the amplitude range of the evoked EPSPs was always adjusted to 2-6 mV (Ͻ30% threshold for generating an action potential). LTP in the perforant path was induced by highfrequency stimulation (HFS) consisting of eight trains, each of eight pulses at 200 Hz with an intertrain interval of 2 sec, as described (29). LTP was operationally defined as Ͼ20% increase above baseline for the amplitude of ESPSs from 26 to 30 min after HFS.…”

Cross talk between Ca2+and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca2+release channels

“…A contribution of RyR, in this case presynaptic, has been suggested by the marked reduction of LTD produced by ryanodine when used at inhibitory concentrations. Interestingly, a switch from LTD to LTP was induced at the hippocampal dentate gyrus by a low stimulatory ryanodine concentration, suggesting that RyR-mediated Ca 2C release plays a significant role in LTP induction (Wang et al 1996).…”

“…Participation of Ca 2C release from intracellular stores in LTP induction has been described (Auerbach & Segal 1994;Wang et al 1996;Reyes-Harde et al 1999;Lu & Hawkins 2002;Lauri et al 2003;Matias et al 2003;Lynch 2004). LTP induction in most hippocampal synapses requires a rise in intracellular postsynaptic [Ca 2C ] mediated by N-methyl-D-aspartate (NMDA) receptors, with contributions from L-type channel activation and intracellular Ca 2C stores (Matias et al 2003;Lynch 2004).…”