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Selective Regulation of xSlo Splice Variants During Xenopus Embryogenesis

¹Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027 Santiago, Chile; ²Department of Physiology and Biophysics, University of Colorado Health Sciences Center, Denver, Colorado 80262; and ³Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Av. J.P. Alessandri 5540, Santiago, Chile

Submitted 22 April 2003; accepted in final form 13 July 2003

Calcium-activated potassium channels regulate excitability of the adult nervous system. In contrast, little is known about the contribution of calcium-activated potassium channels to excitability of the embryonic nervous system when electrical membrane properties and intracellular calcium levels show dramatic changes. Embryonic Xenopus spinal neurons exhibit a well-characterized developmental program of excitability that involves several different currents including calcium-activated ones. Here, we show that a molecular determinant of calcium-activated potassium channels, xSlo, is expressed during Xenopus embryogenesis even prior to differentiation of excitable tissues. Five different xSlo variants are expressed in embryonic tissues as a consequence of alternative exon usage at a single splice site. One of these variants, xSlo59, is neural-specific, and its expression is limited to late stages of neuronal differentiation. However, expression of the four other variants occurs in both muscle and neurons at all stages of development examined. Electrophysiological analysis of recombinant xSlo channels reveals that the xSlo59 exon serves as a gain-of-function module and allows physiologically relevant levels of membrane potential and intracellular calcium to activate effectively the resultant channel. These results suggest that xSlo59 channels play a unique role in sculpting the excitable membrane properties of Xenopus spinal neurons.

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