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J Physiol Volume 544, Number 2, 417-428, October 15, 2002 DOI: 10.1113/jphysiol.2002.025171
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Journal of Physiology (2002), 544.2, pp. 417-428
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.025171

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

Gregory C. Amberg, Salah A. Baker, Sang Don Koh, William J. Hatton *, Keith J. Murray *, Burton Horowitz and Kenton M. Sanders

Department of Physiology and Cell Biology, and *Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557, USA

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 IC50 of 35 µM. 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.



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