Functional Coupling of Ca2+ Channels to Ryanodine Receptors at Presynaptic Terminals: Amplification of Exocytosis and Plasticity

• Published in: The Journal of general physiology 2000-04, Vol.115 (4), p.519-532
• Main Authors: Narita, K., Akita, T., Hachisuka, J., Huang, S.-M., Ochi, K., Kuba, K.
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 0022-1295; 1540-7748
• DOI: 10.1085/jgp.115.4.519

Ca 2+ -induced Ca 2+ release (CICR) enhances a variety of cellular Ca 2+ signaling and functions. How CICR affects impulse-evoked transmitter release is unknown. At frog motor nerve terminals, repetitive Ca 2+ entries slowly prime and subsequently activate the mechanism of CICR via ryanodine receptors and asynchronous exocytosis of transmitters. Further Ca 2+ entry inactivates the CICR mechanism and the absence of Ca 2+ entry for >1 min results in its slow depriming. We now report here that the activation of this unique CICR markedly enhances impulse-evoked exocytosis of transmitter. The conditioning nerve stimulation (10–20 Hz, 2–10 min) that primes the CICR mechanism produced the marked enhancement of the amplitude and quantal content of end-plate potentials (EPPs) that decayed double exponentially with time constants of 1.85 and 10 min. The enhancement was blocked by inhibitors of ryanodine receptors and was accompanied by a slight prolongation of the peak times of EPP and the end-plate currents estimated from deconvolution of EPP. The conditioning nerve stimulation also enhanced single impulse- and tetanus-induced rises in intracellular Ca 2+ in the terminals with little change in time course. There was no change in the rate of growth of the amplitudes of EPPs in a short train after the conditioning stimulation. On the other hand, the augmentation and potentiation of EPP were enhanced, and then decreased in parallel with changes in intraterminal Ca 2+ during repetition of tetani. The results suggest that ryanodine receptors exist close to voltage-gated Ca 2+ channels in the presynaptic terminals and amplify the impulse-evoked exocytosis and its plasticity via CICR after Ca 2+ -dependent priming.