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

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.

GsMTx4-D is a cardioprotectant against myocardial infarction during ischemia and reperfusion

“…We also predict that GsMTx4 buffering of tension in the outer monolayer would transfer tension to the cytoplasmic monolayer. Interestingly, GsMTx4 appears to potentiate 2P domain channels [21] which are found in cardiomyocytes [60,61] and are predicted to have gating elements sensitive to tension changes in the cytoplasmic monolayer [62,63]. …”

Transmural gradients of myocardial structure and mechanics: Implications for fiber stress and strain in pressure overload

“…The potassium channel subfamily K, member 2 (Kcnk2), or 2-pore domain potassium channel TWIK-related K + (TREK-1) has been extensively studied, and is thought to modulate the APD regionally and during sympathetic activation (Bodnár et al, 2015). The TREK-1 gene, mRNA, and protein expression levels were greater in endocardial cells than epicardial cells (Kelly et al, 2006), (Stones et al, 2007), (Tan et al, 2004), (Wang et al, 2013).…”

Two‐Pore K + Channel TREK‐1 Regulates Sinoatrial Node Membrane Excitability

“…TREK‐1 is highly expressed in the nervous system, where it regulates depression phenotypes and nociception. Expression of TREK‐1 has also been identified in heart with proposed roles in regulation of myocyte membrane excitability,7, 8, 9, 10, 11, 12, 13, 14 although its role in specific cardiac phenotypes remains unclear.…”