Ryanodine-sensitive component of calcium transients evoked by nerve firing at presynaptic nerve terminals.

Whether Ca2+ released from stores within the presynaptic nerve terminals also contributes to the Ca2+ elevation evoked by action potentials was tested in intact bullfrog sympathetic ganglia. Intraterminal Ca2+ transients (Delta[Ca2+]i) were evoked by electrical shocks to the presynaptic nerves at 20 Hz and were monitored by fura-2 fluorimetry. Ca2+ released through intraterminal ryanodine-sensitive channels accounted for 46% of the peak Ca2+ elevation. Moreover, in half of the terminals when intraterminal release was blocked by ryanodine, Delta[Ca2+]i reached a plateau at 200 +/- 24 nM. Because 20 Hz is a frequency favorable for the release of a neuropeptide, luteinizing hormone releasing hormone (LHRH) from these presynaptic nerve terminals, and because the threshold level for LHRH release is 186 nM, intraterminal Ca2+ release during nerve firing is likely to play a major role in regulating LHRH release. The intraterminal ryanodine channels were facilitated by caffeine as in other tissue. The releasable ryanodine-sensitive store could elevate the intraterminal [Ca2+] by an amount as high as 1.6 microM at a rate as fast as 250 nM/sec. The store could be refilled within 100 sec after a maximal discharge of its content by 20 Hz firing. Oscillation of [Ca2+]i evoked by 20 Hz nerve firing occurred in normal Ringer solution, in ryanodine, and in caffeine with a periodicity of approximately 10 sec. Besides the facilitatory effects on the ryanodine-sensitive channels, caffeine also had inhibitory effects on Delta[Ca2+]i via its action on a different process.