The intracellular segment of the sodium channel beta 1 subunit is requiredfor its efficient association with the channel alpha subunit

Sodium channels consist of a pore-forming alpha subunit and auxiliary beta1 and beta2 subunits. The subunit beta1 alters the kinetics and voltage-depe ndence of sodium channels expressed in Xenopus oocytes or mammalian cells. Functional modulation in oocytes depends on specific regions in the N-termi nal extracellular domain of beta1, but does not require the intracellular C -terminal domain. Functional modulation is qualitatively different in mamma lian cells, and thus could involve different molecular mechanisms. As a fir st step toward testing this hypothesis, we examined modulation of brain Na( V)1.2a sodium channel alpha subunits expressed in Chinese hamster lung cell s by a mutant beta1 construct with 34 amino acids deleted from the C-termin us. This deletion mutation did not modulate sodium channel function in this cell system. Co-immunoprecipitation data suggest that this loss of functio nal modulation was caused by inefficient association of the mutant beta1 wi th alpha, despite high levels of expression of the mutant protein. In Xenop us oocytes, injection of approximately 10 000 times more mutant beta1 RNA w as required to achieve the level of functional modulation observed with inj ection of full-length beta1. Together, these findings suggest that the C-te rminal cytoplasmic domain of beta1 is an important determinant of beta1 bin ding to the sodium channel alpha subunit in both mammalian cells and Xenopu s oocytes.