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• W2127231749 startingPage "301" @default.
• W2127231749 abstract "Physiological concentrations of 3,5,3'-triiodo-L-thyronine (T3) acutely increased burst-mode gating of Na+ channels in rabbit ventricular myocytes. Bursting was measured as the ratio of long events to the total number of events multiplied by 100 (%LE); a long event was defined as a set of openings or a single opening with a total duration greater than or equal to five times the control mean open time (MOT) for cell-attached patches. In the cell-attached configuration, adding either 5 or 50 nM T3 to the pipette increased the %LE. %LE had a biphasic voltage dependence and peaked at -50 mV, although the largest percentage change from control occurred between -30 and -40 mV. Neither unitary conductance nor the overall MOT was altered by T3-induced bursting. However, the MOT of openings within bursts increased, implying a kinetically distinct mode of channel gating during bursts. Long events sometimes were grouped into runs, but the more usual pattern suggested that modal shifts occurred in approximately 1 second. Similar behavior was observed with triiodothyroacetic acid, a T3 analogue that does not elicit protein synthesis. To investigate involvement of soluble second messengers, cell-attached recordings were made with and without T3 in the bath. Placed outside the pipette, 50 and 100 nM T3 failed to alter MOT, unitary current, or %LE. Na+ channel gating also was unaffected by patch excision and by exposing the cytoplasmic face of inside-out patches to 50 nM T3. Nevertheless, excision to the inside-out configuration with 5 nM T3 in the pipette dramatically increased the %LE and lengthened MOT. These results suggest that T3 induced Na+ channel bursting by an extranuclear mechanism that requires proximity of T3 to the extracellular face of the Na+ channel. Furthermore, T3 was not membrane permeant on the time scale of these experiments. Na+ channel bursting may contribute to the propensity for arrhythmias in hyperthyroidism and to the positive inotropic effect of acute T3 administration in the stunned and ischemic myocardium." @default.
• W2127231749 created "2016-06-24" @default.
• W2127231749 creator A5001634149 @default.
• W2127231749 creator A5003134945 @default.
• W2127231749 date "1993-08-01" @default.
• W2127231749 modified "2023-09-23" @default.
• W2127231749 title "Bursting of cardiac sodium channels after acute exposure to 3,5,3'-triiodo-L-thyronine." @default.
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• W2127231749 doi "https://doi.org/10.1161/01.res.73.2.301" @default.
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