© 1997 American Heart Association, Inc.
Articles |
Alternatively Spliced IS6 Segments of the 
1C Gene Determine the Tissue-Specific Dihydropyridine Sensitivity of Cardiac and Vascular Smooth Muscle L-Type Ca2+ Channels
From the Institut für Pharmakologie und Toxikologie der Technischen Universität München (Germany) (A.W., A.L., N.K., F.H.), and the Institut für Pharmakologie (S.Z., V.F.), Universität des Saarlandes, Homburg/Saar, Germany.
Correspondence to A. Ludwig, Institut für Pharmakologie und Toxikologie der Technischen Universität München, Biedersteiner Straße 29, 80802 München, Germany. E-mail ludwig{at}ipt.med.tu-muenchen.de
Abstract Dihydropyridines (DHPs) block
the vascular smooth muscle L-type Ca2+ channel at lower
concentrations than the cardiac Ca2+ channel, although
their 1 subunit, which binds the DHPs, is derived from
the same gene. This 1C gene gives rise to several splice
variants, among which the 1C-b variant is affected by
lower concentrations of nisoldipine than the 1C-a
variant. Functional expression of chimeras of 1C-a and
1C-b subunits demonstrated that the transmembrane
segment IS6 is responsible for the different
dihydropyridine sensitivity. Northern blot
analysis showed that transcripts coding for the IS6 segment of
the 1C-a subunit were expressed in heart but not in
aorta, whereas the IS6 segment of the 1C-b subunit was
expressed predominantly in vascular smooth muscle. In situ
hybridization of rat heart sections confirmed this expression pattern
of IS6 1C-a and IS6 1C-b in
ventricular and smooth muscle myocytes, respectively. These
results suggest that the different dihydropyridine
sensitivities of cardiac and vascular L-type Ca2+ channels
are caused at least partially by the tissue-specific expression of
alternatively spliced IS6 segments of the 1C gene.
Key Words: Ca2+ antagonist • L-type Ca2+ channel • chimeric channel • heart muscle • vascular smooth muscle
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