Pathways of HERG inactivation Export

@article{citeulike:1648322, abstract = {The rapid, repolarizing K+ current in cardiomyocytes (IKr) has unique inwardly rectifying properties that contribute importantly to the downstroke of the cardiac action potential. The human ether-a-go-go-related gene (HERG) expresses a macroscopic current virtually identical to IKr, but a description of the single-channel properties that cause rectification is lacking. For this reason we measured single-channel and macropatch currents heterologously expressed by HERG in Xenopus oocytes. Our experiments had two main findings. First, the single-channel current-voltage relation showed inward rectification, and conductance was 9.7 pS at [-]100 mV and 3.9 pS at 100 mV when measured in symmetrical 100 mM K+ solutions. Second, single channels frequently showed no openings during depolarization but nevertheless revealed bursts of openings during repolarization. This type of gating may explain the inward rectification of HERG currents. To test this hypothesis, we used a three-closed state kinetics model and obtained rate constants from fits to macropatch data. Results from the model are consistent with rapid inactivation from closed states as a significant source of HERG rectification.}, author = {Kiehn, Johann and Lacerda, Antonio E. and Brown, Arthur M.}, citeulike-article-id = {1648322}, citeulike-linkout-0 = {http://ajpheart.physiology.org/cgi/content/abstract/277/1/H199}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/10409198}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=10409198}, day = {1}, journal = {Am J Physiol Heart Circ Physiol}, keywords = {herg}, month = {July}, number = {1}, pages = {H199--210}, posted-at = {2007-09-12 16:10:42}, priority = {2}, title = {Pathways of HERG inactivation}, url = {http://ajpheart.physiology.org/cgi/content/abstract/277/1/H199}, volume = {277}, year = {1999} }

TY - JOUR ID - citeulike:1648322 L3 - citeulike-article-id:1648322 N2 - The rapid, repolarizing K+ current in cardiomyocytes (IKr) has unique inwardly rectifying properties that contribute importantly to the downstroke of the cardiac action potential. The human ether-a-go-go-related gene (HERG) expresses a macroscopic current virtually identical to IKr, but a description of the single-channel properties that cause rectification is lacking. For this reason we measured single-channel and macropatch currents heterologously expressed by HERG in Xenopus oocytes. Our experiments had two main findings. First, the single-channel current-voltage relation showed inward rectification, and conductance was 9.7 pS at [-]100 mV and 3.9 pS at 100 mV when measured in symmetrical 100 mM K+ solutions. Second, single channels frequently showed no openings during depolarization but nevertheless revealed bursts of openings during repolarization. This type of gating may explain the inward rectification of HERG currents. To test this hypothesis, we used a three-closed state kinetics model and obtained rate constants from fits to macropatch data. Results from the model are consistent with rapid inactivation from closed states as a significant source of HERG rectification. IS - 1 JF - Am J Physiol Heart Circ Physiol EP - 210 TI - Pathways of HERG inactivation VL - 277 SP - H199 KW - herg AU - Kiehn, Johann AU - Lacerda, Antonio AU - Brown, Arthur PY - 1999/07/01/ UR - http://ajpheart.physiology.org/cgi/content/abstract/277/1/H199 ER -