Long-term potentiation of transmitter exocytosis expressed by Ca2+-induced Ca2+ release from thapsigargin-sensitive Ca2+ stores in preganglionic nerve terminals.

We have studied whether Ca(2+)-induced Ca(2+) release (CICR) is involved in the mechanism of long-term potentiation (LTP) at nicotinic synapses of bullfrog sympathetic ganglia. Fast excitatory postsynaptic potentials (fast EPSPs) were recorded in a low-Ca(2+), high-Mg(2+) solution and quantal analysis was applied. The conditioning stimulation of the B-type preganglionic nerve at 20 Hz for 4 min consistently enhanced the amplitude and quantal content of fast EPSP for > 2 h, but only sometimes enhanced the quantal size. The LTP of quantal content produced by the conditioning tetanus was blocked by thapsigargin, a blocker of Ca(2+) pumps at Ca(2+) stores, applied before or after the conditioning tetanus, and by Xestospongin C, a blocker of inositoltrisphosphate (IP(3)) receptors, applied before the tetanus. It was not, however, blocked by ryanodine, a blocker and/or activator of ryanodine receptors, or by propranolol, a blocker of beta-adrenergic receptors. Thus the long-lasting activity of the preganglionic nerve at a high frequency causes the LTP of impulse-evoked transmitter release by the activation of CICR from thapsigargin-sensitive Ca(2+) stores in the nerve terminals. It is likely that a large Ca(2+) entry into the nerve terminals during tetanic activity primes ryanodine-insensitive Ca(2+) release channels for activation.