Modulation of Kv4-encoded K(+) currents in the mammalian myocardium by neuronal calcium sensor-1

J Biol Chem. 2002 Jul 19;277(29):26436-43. doi: 10.1074/jbc.M201431200. Epub 2002 May 6.

Abstract

Voltage-gated K(+) channels are multimeric proteins, consisting of four pore-forming alpha-subunits alone or in association with accessory subunits. Recently, for example, it was shown that the accessory Kv channel interacting proteins form complexes with Kv4 alpha-subunits and modulate Kv4 channel activity. The experiments reported here demonstrate that the neuronal calcium sensor protein-1 (NCS-1), another member of the recoverin-neuronal calcium sensor superfamily, is expressed in adult mouse ventricles and that NCS-1 co-immunoprecipitates with Kv4.3 from (adult mouse) ventricular extracts. In addition, co-expression studies in HEK-293 cells reveal that NCS-1 increases membrane expression of Kv4 alpha-subunits and functional Kv4-encoded K(+) current densities. Co-expression of NCS-1 also decreases the rate of inactivation of Kv4 alpha-subunit-encoded K(+) currents. In contrast to the pronounced effects of Kv channel interacting proteins on Kv4 channel gating, however, NCS-1 co-expression does not measurably affect the voltage dependence of steady-state inactivation or the rate of recovery from inactivation of Kv4-encoded K(+) currents. Taken together, these results suggest that NCS-1 is an accessory subunit of Kv4-encoded I(to,f) channels that functions to regulate I(to,f) density in the mammalian myocardium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae
  • Animals
  • Calcium-Binding Proteins / metabolism*
  • Cell Line
  • Electrophoresis, Polyacrylamide Gel
  • Electrophysiology
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / metabolism*
  • Neuronal Calcium-Sensor Proteins
  • Neuropeptides / metabolism*
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Shal Potassium Channels

Substances

  • Calcium-Binding Proteins
  • Neuronal Calcium-Sensor Proteins
  • Neuropeptides
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Shal Potassium Channels
  • frequenin calcium sensor proteins