Hypotonic-induced stretch counteracts the efficacy of the class III antiarrhythmic agent E-4031 in guinea pig myocytes Export

@article{citeulike:713312, abstract = {Objectives: The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031. Methods: Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patch clamp procedure during perfusion of normotonic, normotonic with addition of E-4031, and hypotonic plus E-4031 solutions. Results: Cell swelling leading to membrane stretch of myocytes in the whole-cell recording configuration occurred with hypotonic solution perfusion. APD, prolonged by E-4031, was reduced to less than control value with hypotonic-induced stretch. Evaluation of whole-cell currents after hypotonic-induced stretch revealed no significant changes in the L-type Ca2+ current, inward rectifier K+ current or the rapid component of the delayed rectifier K+ current. The slow component of the delayed rectifier K+ current (IKs) was upregulated and a stretch-induced CI- current was activated in hypotonic solutions. The hypotonic-induced modulation of these currents was not effected by protein kinase A or C inhibition. Conclusions: Hypotonic-induced stretch shortens APD and counteracts the effects of E-4031. This APD shortening is secondary to upregulation of IKs and activation of a stretch-induced Cl- current.}, author = {Groh, William J. and Gibson, Kevin J. and Maylie, James G.}, citeulike-article-id = {713312}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/0008-6363(95)00106-9}, citeulike-linkout-1 = {http://www.sciencedirect.com/science/article/B6T14-3VXHKBV-14/2/f38e19c009dc143e68d80c12b01e2cb2}, doi = {10.1016/0008-6363(95)00106-9}, journal = {Cardiovascular Research}, keywords = {dilatation-paper}, month = {February}, number = {2}, pages = {237--245}, posted-at = {2006-06-28 03:14:09}, priority = {2}, title = {Hypotonic-induced stretch counteracts the efficacy of the class III antiarrhythmic agent E-4031 in guinea pig myocytes}, url = {http://dx.doi.org/10.1016/0008-6363(95)00106-9}, volume = {31}, year = {1996} }

TY - JOUR ID - citeulike:713312 L3 - citeulike-article-id:713312 N2 - Objectives: The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031. Methods: Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patch clamp procedure during perfusion of normotonic, normotonic with addition of E-4031, and hypotonic plus E-4031 solutions. Results: Cell swelling leading to membrane stretch of myocytes in the whole-cell recording configuration occurred with hypotonic solution perfusion. APD, prolonged by E-4031, was reduced to less than control value with hypotonic-induced stretch. Evaluation of whole-cell currents after hypotonic-induced stretch revealed no significant changes in the L-type Ca2+ current, inward rectifier K+ current or the rapid component of the delayed rectifier K+ current. The slow component of the delayed rectifier K+ current (IKs) was upregulated and a stretch-induced CI- current was activated in hypotonic solutions. The hypotonic-induced modulation of these currents was not effected by protein kinase A or C inhibition. Conclusions: Hypotonic-induced stretch shortens APD and counteracts the effects of E-4031. This APD shortening is secondary to upregulation of IKs and activation of a stretch-induced Cl- current. IS - 2 JF - Cardiovascular Research EP - 245 TI - Hypotonic-induced stretch counteracts the efficacy of the class III antiarrhythmic agent E-4031 in guinea pig myocytes VL - 31 SP - 237 KW - dilatation-paper AU - Groh, William AU - Gibson, Kevin AU - Maylie, James PY - 1996/02// UR - http://dx.doi.org/10.1016/0008-6363(95)00106-9 ER -