This research was supported by the German Research Foundation (DFG; BR 2107/4-1) to Dr. M. Brunner and Dr. K. E. Odening and by the “Margarete von Wrangell Habilitation Program” by the Ministry of Sciences, Research, and Arts in Baden Württemberg and the European Social Fund to Dr. K. E. Odening.
Differential Effects of the β-Adrenoceptor Blockers Carvedilol and Metoprolol on SQT1- and SQT2-Mutant Channels
Article first published online: 29 MAY 2013
© 2013 Wiley Periodicals, Inc.
Journal of Cardiovascular Electrophysiology
Volume 24, Issue 10, pages 1163–1171, October 2013
How to Cite
BODI, I., FRANKE, G., PANTULU, N. D., WU, K., PEREZ-FELIZ, S., BODE, C., ZEHENDER, M., HAUSEN, A. Z., BRUNNER, M. and ODENING, K. E. (2013), Differential Effects of the β-Adrenoceptor Blockers Carvedilol and Metoprolol on SQT1- and SQT2-Mutant Channels. Journal of Cardiovascular Electrophysiology, 24: 1163–1171. doi: 10.1111/jce.12178
- Issue published online: 8 OCT 2013
- Article first published online: 29 MAY 2013
- Accepted manuscript online: 7 MAY 2013 06:36AM EST
- Manuscript Revised: 23 APR 2013
- Manuscript Accepted: 23 APR 2013
- Manuscript Received: 7 MAR 2013
- German Research Foundation. Grant Number: DFG; BR 2107/4-1
Disclaimer: Supplementary materials have been peer-reviewed but not copyedited.
Figure S1. Activation kinetics of WT- and mutant V307L-IKs. (A) Voltage dependence of activation of WT- (n=9-27) and V307L-IKs (n=3–7). Rate of activation was determined by measuring time to half maximal current. Representative current traces illustrating IKs activation at +40 mV in CHO-K1 cells expressing (B) WT- or (C) V307L-KCNQ1. Current traces were normalized to same peak current amplitude.
Figure S2. Representative recordings of time courses of activation of (A) WT- and (B) N588K-IKr. Activation kinetic was measured by using the envelope of tails protocol displayed in the inset: from a holding potential (HP) of −80 mV the cell was depolarized to +40 mV test pulse (TP) for variable duration from 50 milliseconds to 790 milliseconds (50-millisecond increments) before depolarization to −60 mV for 1 second to observe the tail current. (C) The tail current plotted as function of time. Mean average data were fitted with a single exponential function to obtain time constants for activation. All values are presented as mean ± SEM. *P<0.05, **P<0.01.
|jce12178-sup-0003-figuresS3.tif||504K||Figure S3. Fully activated I–V relation of WT- and N588K-IKr. Representative whole-cell current traces recorded from HEK-293T cells transfected with (A) WT- (n=39) or (B) N588K-KCNH2 (n=21) using the voltage protocol in the inset: cells were held at −80 mV and membrane currents were evoked by a double pulse protocol. After a 500-millisecond initial depolarizing voltage step (every 10 seconds) to +40 mV, the cell was repolarized to voltages between −120 mV and +40 mV (20 mV increments) for 500 milliseconds. (C) I–V curve for the peak IKr tail plotted as a function of test potentials.|
|jce12178-sup-0004-figuresS4.tif||653K||Figure S4. Representative current traces of (A) WT- and (B) N588K-IKr depicting differences in inactivation. Voltage protocol is shown in the inset: After an initial long depolarizing pulse (2 seconds) to +40 mV from a holding potential (HP) of −80 mV, a brief (2-millisecond) hyperpolarization step to −100 mV was applied to elicit rapid recovery from inactivation followed by a second depolarizing pulse (2 seconds) to +40 mV to observe “reinactivation.” (C) Bar graph representing inactivated fraction of end-pulse WT- and N588K-IKr at +40 mV. Data are presented as mean ± SEM. *P<0.05, **P<0.01.|
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