OBJECTIVE: The aim is to compare the activation of ATP-sensitive potassium channels (K(ATP) channels) in intact and metabolically impaired atrial and ventricular myocytes. METHODS: The K(ATP) channel current is measured by whole cell and gramicidin-perforated patch clamp recordings in 164 cultured neonate rat cardiomyocytes. RESULTS: In whole cell recordings with 84 micromol/l ADP in pipette, spontaneous activity is significantly higher in atrium than ventricle, and EC(50) for the K(ATP) channel opener diazoxide is 0.13 micromol/l (atrium) versus 3.1 micromol/l (ventricle). With an ATP-regenerating system in pipette, EC(50) for diazoxide is 19.7 micromol/l (atrium) versus 54.9 micromol/l (ventricle). In gramicidin-perforated patch recordings, atrial myocytes respond significantly to 100 nmol/l of the mitochondrial protonophore CCCP, while ventricular myocytes do not. EC(50) for diazoxide is 129 micromol/l (atrium) versus >2500 micromol/l (ventricle) for myocytes exposed to CCCP, and 676 versus >2500 micromol/l, respectively, without CCCP. CONCLUSIONS: (1) K(ATP) channels are significantly more sensitive to metabolic inhibition in atrial than ventricular myocytes. (2) Sensitivity of atrium versus ventricle to the channel opener diazoxide increases from 3:1 to > or = 24:1 with ADP or metabolic inhibition. If extended to intact hearts, the results would predict a higher atrial sensitivity to ischemia, and a high sensitivity of the ischemic atrium to K(ATP) channel openers.
OBJECTIVE: The aim is to compare the activation of ATP-sensitive potassium channels (K(ATP) channels) in intact and metabolically impaired atrial and ventricular myocytes. METHODS: The K(ATP) channel current is measured by whole cell and gramicidin-perforated patch clamp recordings in 164 cultured neonate rat cardiomyocytes. RESULTS: In whole cell recordings with 84 micromol/l ADP in pipette, spontaneous activity is significantly higher in atrium than ventricle, and EC(50) for the K(ATP) channel opener diazoxide is 0.13 micromol/l (atrium) versus 3.1 micromol/l (ventricle). With an ATP-regenerating system in pipette, EC(50) for diazoxide is 19.7 micromol/l (atrium) versus 54.9 micromol/l (ventricle). In gramicidin-perforated patch recordings, atrial myocytes respond significantly to 100 nmol/l of the mitochondrial protonophore CCCP, while ventricular myocytes do not. EC(50) for diazoxide is 129 micromol/l (atrium) versus >2500 micromol/l (ventricle) for myocytes exposed to CCCP, and 676 versus >2500 micromol/l, respectively, without CCCP. CONCLUSIONS: (1) K(ATP) channels are significantly more sensitive to metabolic inhibition in atrial than ventricular myocytes. (2) Sensitivity of atrium versus ventricle to the channel opener diazoxide increases from 3:1 to > or = 24:1 with ADP or metabolic inhibition. If extended to intact hearts, the results would predict a higher atrial sensitivity to ischemia, and a high sensitivity of the ischemic atrium to K(ATP) channel openers.
Authors: Li Bao; Eirini Kefaloyianni; Joshua Lader; Miyoun Hong; Gregory Morley; Glenn I Fishman; Eric A Sobie; William A Coetzee Journal: Circ Arrhythm Electrophysiol Date: 2011-10-09
Authors: Hai Xia Zhang; Jonathan R Silva; Yu-Wen Lin; John W Verbsky; Urvi S Lee; Evelyn M Kanter; Kathryn A Yamada; Richard B Schuessler; Colin G Nichols Journal: Heart Rhythm Date: 2013-07-17 Impact factor: 6.343