A short history of the second messenger concept in neurons and lessons from long lasting changes in two neuronal systems producing afterdischarge and circadian oscillations.

This paper gives a short historical summary of how the second messenger concept, introduced by Earl Sutherland some three decades ago, has been refined and applied by neurobiologists to account for long-lasting changes in the membrane properties of certain neurons. Such refinements in the second messenger hypothesis have application to two specific long-lasting changes in neurons in Aplysia. In the bag cell neuroendocrine system, a brief synaptic input induces an afterdischarge lasting about 30 minutes. Both cAMP-dependent and Ca2+ and phospholipid-dependent protein kinases are activated by the synaptic input and a variety of potassium and calcium channels are modulated. In the eye of Aplysia a spontaneous circadian modulation of ion channels takes place over a twenty-four hour period. In addition phase shifts of this circadian oscillator are mediated, for light by cGMP and for serotonin by cAMP. The circadian oscillator, unlike the bag cell afterdischarge mechanism, is sensitive to ionizing radiation as well as to transcriptional inhibitors. Evidence is presented that specific proteins are synthesized at different times in the circadian cycle. One of these proteins (m.w. 41.9, pI 5.5) accumulates linearly with time of day, resembling a sawtooth oscillator. This protein may be the driver for the circadian oscillation itself. The role of second messengers in various forms of plasticity in neuronal systems (sensitization, long-term potentiation, long-term depression, "learning") may just be part of a very widespread mechanism by which neurons and other cells can generate long-lasting changes in membrane and other cellular properties with brief inputs (synaptic, hormonal) that are of some special adaptive value to the organism.