Alterations in muscarinic K+ channel response to acetylcholine and to G protein-mediated activation in atrial myocytes isolated from failing human hearts

S Koumi, C E Arentzen, C L Backer, J A Wasserstrom
1994 Circulation  
slope conductance of IK(ACh) averaged 42±3 pS (n=28) in HF and 44±2 pS (n=4) in donors, and mean open lifetime was 1.3+±0.3 milliseconds (n=24) in HF and 1.5+±0.4 milliseconds (n=4) in donors. These values were virtually identical in the two groups (not significantly different, NS), although both single IKI and IK(ACh) channel densities were less in HF. Channel open probability of IK(ACh) was also less in HF (4.0+1.2%, n=24) than in donors (6.8+1.1%, n=3, P<.01). The concentration of ACh at
more » ... -maximal activation was 0.11 ,umol/L in HF and 0.03 ,umol/L in donors. In excised insideout patches, IK(ACh) from HF required higher concentrations of GTP and GTPyS to activate the channel compared with donors. These results suggest a reduced lK(ACh) channel sensitivity to M2 cholinergic receptor-linked G protein (G,) in HF compared with donors. Conclusions Atrial myocytes isolated from failing human hearts exhibited a lower resting membrane potential and reduced sensitivity to ACh compared with donor atria. Wholecell and single-channel measurements suggest that these alterations are caused by reduced IK1 and IK(ACh) channel density and reduced lK(ACh) channel sensitivity to Gi-mediated channel activation in HF. (Circulation. 1994;90:2213-2224
doi:10.1161/01.cir.90.5.2213 pmid:7955176 fatcat:r3qqdsnt4jdjfdr352whkvp5wm