Control of secretion by temporal patterns of action potentials in adrenal chromaffin cells

Action potentials (APs) are the principal physiological stimuli for neurotransmitter secretion in neurons. Most studies on stimulus-secretion coupling have been performed under voltage clamp using artificial electrical stimuli. To investigate the modulatory effects of AP codes on neural secretion, we introduce a capacitance method to study AP-induced secretion in single cells. The action potential pattern was defined by a four-parameter "code function:" F(n, m, f, d). With this method, cell secretion evoked by stimulation with an AP code was quantified in real time by membrane capacitance (Cm) in adrenal chromaffin cells. We found, in addition to AP frequency (f), for a given number of APs, another parameter of the AP code, the number of AP bursts (m) in which the set of APs occurs, can effectively modulate cell secretion. Possible mechanisms of the m effect are depletion of the readily releasable pool and inactivation of Ca2+ channels during a burst of APs. The physiological m effect may play a key role in AP-mediated neural information transfer within a single neuron and among the elements of a neural network.