Suppression of electrical alternans by ...

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Title Suppression of electrical alternans by overexpression of HERG in canine ventricular myocytes
Author(s) Fei Hua, David C. Johns, Robert F.,,Jr Gilmour
Journal American Journal of Physiology. Heart and Circulatory Physiology
Date 2004
Volume 286
Issue 6
Start page 2342
End page H2351
Abstract Suppression of electrical alternans may be antiarrhythmic. Our previous computer simulations have suggested that increasing the rapid component of the delayed rectifier K(+) current (I(Kr)) suppresses alternans. To test this hypothesis, I(Kr) in isolated canine ventricular myocytes was increased by infection with an adenovirus containing the gene for the pore-forming domain of I(Kr) human ether-a-go-go gene (HERG)]. With the use of the perforated or whole cell patch-clamp technique, action potentials recorded at different pacing cycle lengths (CLs) were applied to the myocytes as the command waveforms. HERG infection markedly increased peak I(Kr) during the action potential (from 0.54 +/- 0.03 pA/pF in control to 3.60 +/- 0.81 pA/pF). Rate-dependent alterations of peak I(Kr) were similar for freshly isolated myocytes and HERG-infected myocytes. In both cell types, I(Kr) increased when CL decreased from 1,000 to 500 ms and then decreased progressively as CL decreased further. During alternans at CL = 170 ms, peak I(Kr) was larger for the short than for the long action potential for both groups, but the difference in peak I(Kr) was larger for HERG-infected myocytes. The voltage at which peak I(Kr) occurred was significantly less negative in HERG-infected myocytes, in association with shifts of the steady-state voltage-dependent activation and inactivation curves to less negative potentials. Pacing at short CL induced stable alternans in freshly isolated myocytes and in cultured myocytes without HERG infection, but not in HERG-infected myocytes. These data support the idea that increasing I(Kr) may be a viable approach to suppressing electrical alternans.
DOI 10.1152/ajpheart.00793.2003

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