M. Muschol et Bm. Salzberg, Dependence of transient and residual calcium dynamics on action-potential patterning during neuropeptide secretion, J NEUROSC, 20(18), 2000, pp. 6773-6780
Secretion of the neuropeptide arginine vasopressin (AVP) from the neurohypo
physis is optimized by short phasic bursts of action potentials with a mean
intraburst frequency around 10 Hz. Several hypotheses, most prominently ac
tion-potential broadening and buildup of residual calcium, have been propos
ed to explain this frequency dependence of AVP release. However, how either
of these mechanisms would optimize release at any given frequency remains
an open question. We have addressed this issue by correlating the frequency
-dependence of intraterminal calcium dynamics and AVP release during action
-potential stimulation.
By monitoring the intraterminal calcium changes with low-affinity indicator
dyes and millisecond time resolution, the signal could be dissected into t
hree separate components: rapid Ca2+ rises (Delta[Ca2+](tr)) related to act
ion-potential depolarization, Ca2+ extrusion and/or uptake, and a gradual i
ncrease in residual calcium (Delta D[Ca2+](res)) throughout the stimulus tr
ain. Action-potential stimulation modulated all three components in a manne
r dependent on both the stimulation frequency and number of stimuli. Overal
l, the cumulative Delta[Ca2+](tr) amplitude initially increased with f(Stim
) and then rapidly deteriorated, with a maximum around f(Stim) less than or
equal to 5 Hz. Residual calcium levels, in contrast, increased monotonical
ly with stimulation frequency.
Simultaneously with the calcium measurements we determined the amount of AV
P release evoked by each stimulus train. Hormone release increased with fSt
im beyond the peak in Delta[Ca2+](tr) amplitudes, reaching its maximum betw
een 5 and 10 Hz before returning to its 1 Hz level. Thus, AVP release respo
nds to the temporal patterning of stimulation, is sensitive to both Delta[C
a2+](tr) and Delta[Ca2+](res), and is optimized at a frequency intermediate
between the frequency-dependent maxima in Delta[Ca2+](tr) and Delta[Ca2+](
res).