The control of early development of neuronal excitability

8 THE CONTROL OF BARLY DEVELOPMENT OF NEURONAL EXCITABILITY Nicholas C. Spitzer. Biology Department, Univ. of Calif., San Diego, La Jolla, CA The acquisition and early maturation of specialized membrane properties has now been examined in a variety of neurons. The onset of electrical excitability, neurotransmitter sensitivity and electrical uncoupling have been investigated, and some general features of differentiation emerge. The action potential often has a prominent Ca component initially that later disappears as the impulse shortens and becomes principally Na-dependent; cells that are initially electrically coupled become uncoupled; the ionic dependence of responses to neurotransmitters is constant during development, in spite of changes in the number and distribution of receptors. Rohon-Beard neurons in the amphibian spinal cord have been useful for these studies, partly because much of the differentiation that occurs in vivo occurs in dissociated cell cultures as well, in -the absence of intercellular contacts. These cultures provide an opportunity to investigate the mechanisms controlling the early developmental sequence of events. The possibility that the functional expression of early phenotypes influences the appearance of those arising later has been examined by growing cells in Ca-free medium to block Ca-dependent action potentials. The possibility that RNA and protein synthesis are necessary for the expression of these phenotypes has been examined by application of specific metabolic inhibitors for brief periods during neuronal development. The findings will be compared with the results of investigations of the later maturation and maintenance of excitability, which may be governed by other rules. Supported by NS 15918 from NIH.