Vol. 182, No. 2, 1992 January 31, 1992 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 794-801 SEQUENCE AND GENOMIC STRUCTURE OF THE HUMAN ADULT SKELETAL MUSCLE SODIUM CHANNEL QISUBUNIT GENE ON 17q Jianzhou Wang, Cecilia V. Rojas, Jianhua Zhou, Lisa S. Schwartz, Hugh Nicholas’, and Eric P. Hoffman Departments of Molecular Genetics and Biochemistry, Human Genetics, and Pediatrics * Pittsburgh Supercomputer Center University of Pittsburgh School of Medicine, Pittsburgh PA 15261 Received December 12, 1991 The ammo acid sequence of the sodium channel (Ysubunit from adult human skeletal muscle has been deduced by cross-species PCR-mediated cloning and sequencing of the cDNA. The protein consists of 1836 amino acid residues. The amino acid sequence shows 93% identity to the (r subunit from rat adult skeletal muscle and 70% identity to the (Y subunit from other mammalian tissues. A 500 kb YAC clone containing the complete coding sequence and two overlapping lambda clones covering 68% of the cDNA were used to estimate the gene size at 35 kb. The YAC clone proved crucial for gene structure studies as the high conservation between ion channel genes made hybridization studies with total genomic DNA difficult. Our results provide valuable information for the study of periodic paralysis and paramyotonia congenita, two inherited neurological disorders which are caused by point mutations within this gene. 0 1992 Academic Press, Inc. Voltage-gated sodium channels conduct the inward sodium current responsible for the propagation of the action potential in most excitable membranes (1). Several sodium channel isoforms are expressed in specific tissues or during defined developmental stages (2). The purified sodium channel protein from mammalian skeletal muscle consists of two subunits, a 260 KD (Ysubunit and a 8 subunit of 38 KD (6). The large 01 subunit alone has the functional properties of the native channel from muscle and from other tissues, as demonstrated by in vitro reconstitution and expression experiments (3,4,5,6,7,8,9). Two distinct mRNAs that encode sodium channel (Ysubunits have been cloned and sequenced from rat skeletal muscle, one present in adult skeletal muscle (8), and the second in fetal/ neonatal skeletal muscle and after denervation (9). 0006-291X/92 $1.50 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved. 794