tailieunhanh - Báo cáo khoa học: Molecular cloning and functional expression of the human sodium channel b1B subunit, a novel splicing variant of the b1 subunit

The voltage gated sodiumchannel comprises apore-forming asubunit and regulatory bsubunits. We report here the identificationandcharacterizationof anovel splicingvariant of the humanb1 subunit, termed b1B. The 807 bp open reading frame of the human b1Bsubunit encodes a 268 residue protein with a calculated molecular mass of kDa. The novel humanb1B subunit shares an identical N-terminal half (residues 1–149) with the humanb1subunit, but contains a novel C-terminal half (residues 150–268) of less than 17%sequence identity with the humanb1 subunit | Eur. J. Biochem. 270 4762-4770 2003 FEBS 2003 doi Molecular cloning and functional expression of the human sodium channel p1B subunit a novel splicing variant of the b1 subunit Ning Qin1 Michael R. D Andrea1 Mary-Lou Lubin1 Navid Shafaee2 Ellen E. Codd1 and Ana M. Correa2 1 Department of Drug Discovery Johnson Johnson Pharmaceutical Research Development Spring House PA USA department of Anesthesiology University of California Los Angeles CA USA The voltage gated sodium channel comprises a pore-forming a subunit and regulatory b subunits. We report here the identification and characterization of a novel splicing variant of the human b1 subunit termed b1B. The 807 bp open reading frame of the human b1B subunit encodes a 268 residue protein with a calculated molecular mass of kDa. The novel human b1B subunit shares an identical N-terminal half residues 1-149 with the human b1 subunit but contains a novel C-terminal half residues 150-268 of less than 17 sequence identity with the human b1 subunit. The C-terminal region of the human b1B is also significantly different from that of the rat b1A subunit sharing less than 33 sequence identity. Tissue distribution studies reveal that the human b1B subunit is expressed predominantly in human brain spinal cord dorsal root ganglion and skeletal muscle. Functional studies in oocytes demonstrate that the human b1B subunit increases the ionic current when coexpressed with the tetrodotoxin sensitive channel without significantly changing voltage dependent kinetics and steady-state properties thus distinguishing it from the human b1 and rat b1A subunits. Keywords sodium channel b1B subunit splicing variant. By mediating the rapid entry of sodium ions into excitable cells in response to voltage changes across the plasma membrane voltage gated sodium channels VGSCs play a fundamental role in the control of neuronal excitability in the central and peripheral nervous systems. The VGSC is a .