A human calcium-activated potassium channel gene expressed in
vascular smooth muscle.
McCobb, David P., Natalie L. Fowler, Terence Featherstone, Christopher
J. Lingle, Mitsuyoshi Saito, James E. Krause, and Lawrence Salkoff.
Department of Anatomy and Neurobiology, Department of Genetics,
Department of Anesthesiology, Washington University Medical School,
St. Louis, MO 63110
APStracts 2:0114H, 1995.
Large-conductance calcium-activated potassium (BK) channels are
widespread and functionally heterogeneous. In other classes of K
channels, functional heterogeneity derives from large gene families,
alternative splicing, heterologous subunit composition, and
functional modulation. The molecular basis of mammalian BK channel
heterogeneity is unknown, since only a single gene (mSlo) has been
identified. BK channels in native vascular smooth muscle have an
apparent calcium-sensitivity 10 fold greater than native brain or
skeletal muscle channels, or cloned mSlo channels. Using mSlo as a
low-stringency probe we screened human arterial smooth muscle and
genomic libraries extensively in search of genes or splice variants
with novel properties. We isolated the human homologue of mSlo,
including 2 novel splice variant forms, but found no other related
genes. Electrophysiological characterization of the hSlo clones in
Xenopus oocytes and Chinese hamster ovary cells gave BK currents that
were not measurably different from mSlo currents. However,
coexpression of hSlo with a recently cloned -subunit derived from
smooth muscle dramatically increased apparent calcium sensitivity.
Thus alpha subunits alone may not determine calcium sensitivity of
vascular smooth muscle BK channels. HSlo was mapped to human
chromosome 10q23.1, and genomic structure was analyzed. Immediately
following the amino terminal, two unusual regions of trinucleotide
repeating sequences are present. The first of these regions encodes,
polyglycine; the second, polyserine. Both regions of repeated
sequence are conserved between the mouse and human genome.
Received 7 November 1994; accepted in final form 1 March 1995.
APS Manuscript Number H994-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.