Characterization of the A-type potassium current in murine gastric antrum.
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.
Amberg
Gregory C
GC
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Baker
Salah A
SA
Koh
Sang Don
SD
Hatton
William J
WJ
Murray
Keith J
KJ
Horowitz
Burton
B
Sanders
Kenton M
KM
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D004553:Electric Conductivity; D005424:Flecainide / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms / Q000378:metabolism; D011706:Pyloric Antrum / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051672:Shal Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology
C497019:Kcnd2 protein, mouse; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D051672:Shal Potassium Channels; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D005424:Flecainide