title: G protein-activated (GIRK) current in rat ventricular myocytes is masked by constitutive inward rectifier current (I(K1)).
abstract: Inwardly-rectifying K+ channel subunits are not homogenously expressed in different cardiac tissues. In ventricular myocytes (VM) the background current-voltage relation is dominated by I(K1), carried by channels composed of Kir2.x subunits, which is less important in atrial myocytes (AM). On the other hand in AM a large G protein gated current carried by Kir3.1/3.4 complexes can be activated by stimulation of muscarinic M(2) receptors (I(K(ACh))), which is assumed to be marginal in VM. Recent evidence suggests that total current carried by cardiac inward-rectifiers (I(K(ATP)), I(K(ACh)), I(K1)) in both, AM and VM is limited, due to K+ accumulation/depletion. This lead us to hypothesize that in conventional whole celI recordings I(K(ACh)) in VM is underestimated as a consequence of constitutive I(K1). In that case a reduction in density of I(K1) should be paralleled by an increase in density of I(K(ACh)). Three different experimental strategies have been used to test for this hypothesis: (i) Adenovirus-driven expression of a dominant-negative mutant of Kir2.1, one of the subunits supposed to form I(K1) channels, in VM caused a reduction in I(K1)-density by about 80 %. In those cells I(K(ACh)) was increased about 4 fold. (ii) A comparable increase in I(K(ACh)) was observed upon reduction of I(K1) caused by adenovirus-mediated RNA interference.(iii) Ba2+ in a concentration of 2 microM blocks I(K1) in VM by about 60 % without affecting atrial I(K(ACh)). The reduction in I(K1) by 2 microM Ba2+ is paralleled by a reversible increase in I(K(ACh)) by about 100%. These data demonstrate that the increase in K+ conductance underlying ventricular I(K(ACh)) is largely underestimated, suggesting that it might be of greater physiological relevance than previously thought.
authors.affiliation: Institute of Physiology, Ruhr-University Bochum, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beckmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Rinne
authors.forename: Christoph
authors.initials: C
authors.lastname: Littwitz
authors.forename: Elisa
authors.initials: E
authors.lastname: Mintert
authors.forename: Leif I
authors.initials: LI
authors.lastname: Bosche
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Kienitz
authors.forename: Lutz
authors.initials: L
authors.lastname: Pott
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bender
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D034741:RNA, Small Interfering