| dc.contributor.author | Missan, Sergey. | en_US |
| dc.date.accessioned | 2014-10-21T12:36:36Z | |
| dc.date.available | 2006 | |
| dc.date.issued | 2006 | en_US |
| dc.identifier.other | AAINR16701 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/54794 | |
| dc.description | The slow component of cardiac delayed-rectifier potassium current ( IKs) is active under physiological conditions in guinea pig ventricular cardiac myocytes and plays a role in myocyte action potential plateau termination and membrane repolarization. IKs is stimulated by application of hyposmotic external solution and inhibited by application of hyperosmotic solution. The mechanism responsible for this modulation remains largely unknown. The goal of the present study was to investigate the role of tyrosine phosphorylation/dephosphorylation in the stimulation of IKs by hyposmotic solution and to obtain pertinent information on regulation of IKs under isosmotic conditions. | en_US |
| dc.description | Application of hyposmotic (0.75T) solution increased the amplitude of IKs by 73%, with little effect on current kinetics and the voltage-dependence of activation. Protein kinase A (PKA), protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3-K), MAP kinase (ERK1/2), G-proteins, and the cytoskeleton appear not to be involved in the stimulation of IKs by hyposmotic solution. On the other hand, broadspectrum protein tyrosine kinase (PTK) inhibitors genistein, tyrphostin A23, and tyrphostin A25 strongly decreased the amplitude of IKs under isosmotic conditions with EC50 values of 64, 4.1, and 12.3 mum, respectively. These inhibitors also blunted stimulation of the current by hyposmotic solution. Src PTK inhibitor PP2 decreased I Ks under isosmotic conditions and attenuated hyposmotic stimulation of IKs, whereas epidermal growth factor receptor (EGFR) inhibitor tyrphostin AG1478 had neither of these effects. PTK-inactive analogues of genistein (genistin and daidzein), tyrphostins (A1 and A63), and PP2 (PP3) had little or no inhibitory influence on I Ks. | en_US |
| dc.description | The phosphotyrosyl phosphatase (PTP) inhibitors orthovanadate (1 mM) and DMHV (100 muM) had little effect on IKs under control conditions. However, they rapidly reversed the inhibitory effects of genistein, A23, and A25 on IKs. These results suggest that IKs in guinea pig ventricular myocytes is strongly modulated by PTK/PTP under isosmotic conditions, and that the stimulation of IKs by hyposmotic solution depends on Src-type PTK activity. Stimulation of IKs under hyposmotic conditions decreases action potential duration, a potential antiarrhythmogenic effect. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2006. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Cell. | en_US |
| dc.subject | Biology, Physiology. | en_US |
| dc.subject | Biophysics, General. | en_US |
| dc.title | Volume-sensitive potassium(+) current in guinea pig ventricular myocytes. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
