Characterization of the A-type potassium current in murine gastric antrum

J Physiol. 2002 Oct 15;544(2):417-28. doi: 10.1113/jphysiol.2002.025171.

Abstract

A-type currents are rapidly inactivating potassium currents that operate at subthreshold potentials. A-type currents have not been reported to occur in the phasic muscles of the stomach. We used conventional voltage-clamp techniques to identify and characterize A-type currents in myocytes isolated from the murine antrum. A-type currents were robust in these cells, with peak current densities averaging 30 pA pF(-1) at 0 mV. These currents underwent rapid inactivation with a time constant of 83 ms at 0 mV. Recovery from inactivation at -80 mV was rapid, with a time constant of 252 ms. The A-type current was blocked by 4-aminopyridine (4-AP) and was inhibited by flecainide, with an IC(50) of 35 microM. The voltage for half-activation was -26 mV, while the voltage of half-inactivation was -65 mV. There was significant activation and incomplete inactivation at potentials positive to -60 mV, which is suggestive of sustained current availability in this voltage range. Under current-clamp conditions, exposure to 4-AP or flecainide depolarized the membrane potential by 7-10 mV. In intact antral tissue preparations, flecainide depolarized the membrane potential between slow waves by 5 mV; changes in slow waves were not evident. The effect of flecainide was not abolished by inhibiting enteric neurotransmission or by blocking delayed rectifier and ATP-sensitive K(+) currents. Transcripts encoding Kv4 channels were detected in isolated antral myocytes by RT-PCR. Immunocytochemistry revealed intense Kv4.2- and Kv4.3-like immunoreactivity in antral myocytes. These data suggest that the A-type current in murine antral smooth muscle cells is likely to be due to Kv4 channels. This current contributes to the maintenance of negative resting membrane potentials.

Publication types

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

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Electric Conductivity
  • Flecainide / pharmacology
  • Membrane Potentials
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Smooth / physiology
  • Myocytes, Smooth Muscle / metabolism
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated*
  • Protein Isoforms / metabolism
  • Pyloric Antrum / cytology
  • Pyloric Antrum / metabolism*
  • Pyloric Antrum / physiology
  • Shal Potassium Channels
  • Tetraethylammonium / pharmacology

Substances

  • Kcnd2 protein, mouse
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Protein Isoforms
  • Shal Potassium Channels
  • Tetraethylammonium
  • 4-Aminopyridine
  • Flecainide