Cell
Volume 104, Issue 2, 26 January 2001, Pages 217-231
Journal home page for Cell

Article
MiRP2 Forms Potassium Channels in Skeletal Muscle with Kv3.4 and Is Associated with Periodic Paralysis

https://doi.org/10.1016/S0092-8674(01)00207-0Get rights and content
Under an Elsevier user license
open archive

Abstract

The subthreshold, voltage-gated potassium channel of skeletal muscle is shown to contain MinK-related peptide 2 (MiRP2) and the pore-forming subunit Kv3.4. MiRP2-Kv3.4 channels differ from Kv3.4 channels in unitary conductance, voltage-dependent activation, recovery from inactivation, steady-state open probability, and block by a peptide toxin. Thus, MiRP2-Kv3.4 channels set resting membrane potential (RMP) and do not produce afterhyperpolarization or cumulative inactivation to limit action potential frequency. A missense mutation is identified in the gene for MiRP2 (KCNE3) in two families with periodic paralysis and found to segregate with the disease. Mutant MiRP2-Kv3.4 complexes exhibit reduced current density and diminished capacity to set RMP. Thus, MiRP2 operates with a classical potassium channel subunit to govern skeletal muscle function and pathophysiology.

Cited by (0)