High Temperature Sensitivity Is Intrinsic to Voltage-Gated Potassium Channels

Elife. 2014 Jul 16;3:e03255. doi: 10.7554/eLife.03255.

Abstract

Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. Therefore, high temperature sensitivity is intrinsic to both TRP and Kv channels. Our findings suggest important physiological roles of heat-induced variation in Kv channel activities. Mechanistically our findings indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain; instead, non-obligatory allosteric gating permits the intrinsic heat sensitivity to drive channel activation, allowing temperature-sensitive TRP channels to function as polymodal nociceptors.

Keywords: TRP channel; allosteric coupling; conformational changes; gating; potassium channel; temperature sensing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Animals
  • Gene Expression
  • HEK293 Cells
  • Hot Temperature
  • Humans
  • Ion Channel Gating
  • Ion Transport
  • Large-Conductance Calcium-Activated Potassium Channels / chemistry*
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Membrane Potentials / physiology
  • Mice
  • Patch-Clamp Techniques
  • Potassium / metabolism*
  • Protein Structure, Tertiary
  • Shab Potassium Channels / chemistry*
  • Shab Potassium Channels / genetics
  • Shab Potassium Channels / metabolism
  • Shaker Superfamily of Potassium Channels / chemistry*
  • Shaker Superfamily of Potassium Channels / genetics
  • Shaker Superfamily of Potassium Channels / metabolism
  • Shal Potassium Channels / chemistry*
  • Shal Potassium Channels / genetics
  • Shal Potassium Channels / metabolism
  • TRPV Cation Channels / chemistry*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Transgenes

Substances

  • Kcnb1 protein, mouse
  • Large-Conductance Calcium-Activated Potassium Channels
  • Shab Potassium Channels
  • Shaker Superfamily of Potassium Channels
  • Shal Potassium Channels
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Potassium