Temperature sensitivity of two-pore (K2P) potassium channels

Abstract

At normal body temperature, the two-pore potassium channels TREK-1 (K2P2.1/KCNK2), TREK-2 (K2P10.1/KCNK10), and TRAAK (K2P4.1/KCNK2) regulate cellular excitability by providing voltage-independent leak of potassium. Heat dramatically potentiates K2P channel activity and further affects excitation. This review focuses on the current understanding of the physiological role of heat-activated K2P current, and discusses the molecular mechanism of temperature gating in TREK-1, TREK-2, and TRAAK.

Keywords: Ion channel; K(2P); Potassium channel; TRAAK; TREK-1; TREK-2; Thermosensitivity; Thermotransduction; Two-pore.

Figure 5.1

Membrane topology of K2P channels. (A) A topology diagram of a single K_2P subunit with two pore-forming domains. (B) A mature channel is formed by two subunits covalently linked via the cysteines (C) in the first extracellular loop. M1–M4, trans-membrane segment 1–4; P1–2, pore helix 1–2. (See the color plate.)

Figure 5.2

A comparison of temperature activation profiles between TREK-1 and TRPV1. (A) Current–voltage plots showing the activity of TREK-1 and TRPV1 recorded by two-electrode voltage clamp in Xenopus oocytes at different temperatures. Currents were evoked in a “physiological” solution (2 mM KCl, 96 mM NaCl, 1.8 mM CaCl₂, 2 mM MgCl₂, 5 mM HEPES pH 7.4) by a 1-s-long voltage ramp from a holding potential of −80 mV. (B) Normalized activity of TREK-1 and TRPV1 at different temperatures, measured at 40 mV.

Figure 5.3

A hypothetical cartoon model of how Ct affects TREK-1 activity. A cartoon model of a single TREK-1 subunit showing a hypothetical mechanism of channel activation by temperature. It was proposed that increasing temperature facilitates the transition of Ct from inactive to active conformation, leading to stabilization of an open conformation of the selectivity filter via interaction between Trp275 (W) and Gly137 (G) from a single TREK-1 subunit (Bagriantsev et al., 2012). M1–M4, transmembrane segment 1–4; P1–2, pore helix 1–2; Ct, C-terminal domain. Blue spheres depict potassium ions. (See the color plate.)