In:
The Journal of Physiology, Wiley, Vol. 550, No. 2 ( 2003-07), p. 365-372
Abstract:
Cardiac inward rectifier K + currents ( I K1 ) play an important role in maintaining resting membrane potential and contribute to late phase repolarization. Members of the K ir2.x channel family appear to encode for I K1 . The purpose of this study was to determine the molecular composition of cardiac I K1 in rabbit ventricle. Western blots revealed that K ir2.1 and K ir2.2 , but not K ir2.3 , are expressed in rabbit ventricle. Culturing rabbit myocytes resulted in a ∼50 % reduction of I K1 density after 48 or 72 h in culture which was associated with an 80 % reduction in K ir2.1 , but no change in K ir2.2 , protein expression. Dominant‐negative (DN) constructs of K ir2.1 , K ir2.2 and K ir2.3 were generated and tested in tsA201 cells. Adenovirus‐mediated over‐expression of K ir2.1dn , K ir2.2dn or K ir2.1dn plus K ir2.2dn in cultured rabbit ventricular myocytes reduced I K1 density equally by 70 % 72 h post‐infection, while AdK ir2.3dn had no effect, compared to green fluorescent protein (GFP)‐infected myocytes. Previous studies indicate that the [Ba 2+ ] required for half‐maximum block (IC 50 ) differs significantly between K ir2.1 , K ir2.2 and K ir2.3 channels. The dependence of I K1 on [Ba 2+ ] revealed a single binding isotherm which did not change with time in culture. The IC 50 for block of I K1 was also unaffected by expression of the different DN genes after 72 h in culture. Taken together, these results demonstrate functional expression of K ir2.1 and K ir2.2 in rabbit ventricular myocytes and suggest that macroscopic I K1 is predominantly composed of K ir2.1 and K ir2.2 heterotetramers.
Type of Medium:
Online Resource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/jphysiol.2002.036400
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
1475290-6
SSG:
12
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