KCNQ5, a Novel Potassium Channel Broadly Expressed in Brain, Mediates M-type Currents*

  1. Thomas J. Jentsch§
  1. From the Zentrum für Molekulare Neurobiologie Hamburg, Hamburg University, Martinistrasse 85, D-20246 Hamburg, Germany

Abstract

KCNQ2 and KCNQ3, both of which are mutated in a type of human neonatal epilepsy, form heteromeric potassium channels that are expressed in broad regions of the brain. The associated current may be identical to the M-current, an important regulator of neuronal excitability. We now show that the RNA encoding the novel KCNQ5 channel is also expressed in brain and in sympathetic ganglia where it overlaps largely with KCNQ2 and KCNQ3. In addition, it is expressed in skeletal muscle. KCNQ5 yields currents that activate slowly with depolarization and can form heteromeric channels with KCNQ3. Currents expressed from KCNQ5 have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. A KCNQ5 splice variant found in skeletal muscle displays altered gating kinetics. This indicates a molecular diversity of channels yielding M-type currents and suggests a role for KCNQ5 in the regulation of neuronal excitability.

  • Abbreviations:
    BFNC
    benign familial neonatal convulsions
    TEA
    tetraethylammonium
    WT
    wild type
    PCR
    polymerase chain reaction
    • Received April 17, 2000.
    • Revision received May 16, 2000.
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