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Characterization of the A‐type potassium current in murine gastric antrum
Author(s) -
Amberg Gregory C.,
Baker Salah A.,
Koh Sang Don,
Hatton William J.,
Murray Keith J.,
Horowitz Burton,
Sanders Kenton M.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.025171
Subject(s) - antrum , patch clamp , membrane potential , chemistry , biophysics , flecainide , voltage clamp , potassium channel , time constant , myocyte , reversal potential , medicine , endocrinology , electrophysiology , stomach , biology , biochemistry , atrial fibrillation , engineering , electrical engineering
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 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.