G Protein-Activated (GIRK) Current in Rat Ventricular Myocytes is Masked by Constitutive Inward Rectifier Current (IK1)

• Published in: Cellular physiology and biochemistry Vol. 21; no. 4; pp. 259 - 268
• Main Authors: Beckmann, Christian, Rinne, Andreas, Littwitz, Christoph, Mintert, Elisa, Bösche, Leif I., Kienitz, Marie-Cécile, Pott, Lutz, Bender, Kirsten
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01-01-2008
• Subjects: Animals; Arteries - metabolism; Cell Survival; Cells, Cultured; Electrophysiology; G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Original Paper; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying - genetics; Potassium Channels, Inwardly Rectifying - metabolism; Rats; RNA, Small Interfering - genetics; K+ channel; Gene transfer; Inward rectifier; GIRK; siRNA; Cardiac myocytes; Kir2, Kir3
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000129381

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) Ba 2+ in a concentration of 2 µM blocks I K1 in VM by about 60 % without affecting atrial I K(ACh) . The reduction in I K1 by 2 µM Ba 2+ 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.