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The potassium current carried by TREK-1 channels in rat cardiac ventricular muscle

  • Ion channels, receptors and transporters
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Abstract

We studied the potassium current flowing through TREK-1 channels in rat cardiac ventricular myocytes. We separated the TREK-1 current from other current components by blocking most other channels with a blocker cocktail. We tried to inhibit the TREK-1 current by activating protein kinase A (PKA) with a mixture of forskolin and isobutyl-methylxanthine (IBMX). Activation of PKA blocked an outwardly rectifying current component at membrane potentials positive to −40 mV. At 37 °C, application of forskolin plus IBMX reduced the steady-state outward current measured at positive voltages by about 52 %. Application of the potassium channel blockers quinidine or tetrahexylammonium also reduced the steady-state outward current by about 50 %. Taken together, our results suggest that the increase in temperature from 22 to 37 °C increased the TREK-1 current by a factor of at least 5 and that the average density of the TREK-1 current in rat cardiomyocytes at 37 °C is about 1.5 pA/pF at +30 mV. The contribution of TREK-1 to the action potential was assessed by using a dynamic patch clamp technique. After subtraction of simulated TREK-1 currents, action potential duration at 50 or 90 % repolarisation was increased by about 12 %, indicating that TREK-1 may be functionally important in rat ventricular muscle. During sympathetic stimulation, inhibition of TREK-1 channels via PKA is expected to prolong the action potential primarily in subendocardial myocytes; this may decrease the transmural dispersion of repolarisation and thus may serve to prevent the occurrence of arrhythmias.

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Acknowledgments

We thank Brigitte Burk for excellent technical support. This study was supported by the Deutsche Forschungsgemeinschaft (FOR 1086, TP7).

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  1. Institute of Physiology and Pathophysiology, Marburg University, 35037, Marburg, Germany

    Mandy Bodnár, Günter Schlichthörl & Jürgen Daut

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  1. Mandy Bodnár
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  2. Günter Schlichthörl
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Correspondence to Jürgen Daut.

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This article is published as part of the special issue on K2P channels.

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Bodnár, M., Schlichthörl, G. & Daut, J. The potassium current carried by TREK-1 channels in rat cardiac ventricular muscle. Pflugers Arch - Eur J Physiol 467, 1069–1079 (2015). https://doi.org/10.1007/s00424-014-1678-9

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