Submitted on July 13, 2004
Accepted on January 26, 2005
Regional differences in cholinergic regulation of potassium current in feline esophageal circular smooth muscle
Ahmad Muinuddin1, Khurram Naqvi2, Laura Sheu3, Herbert Y. Gaisano4, and Nicholas E. Diamant1*
1 Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; University Health Network, University of Toronto, Toronto, Ontario, Canada
2 University Health Network, University of Toronto, Toronto, Ontario, Canada
3 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
4 Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: ndiamant{at}uhnres.utoronto.ca.
Potassium channels are important contributors to membrane excitability in
smooth muscles. There are regional differences in resting membrane potential (RMP) and
K+ channel density along the length of the feline circular smooth muscle esophagus. The
aim of this study was to assess responses of K+ channel currents to cholinergic (ACh)
stimulation along the length of the feline circular smooth muscle esophageal body.
Perforated patch clamp technique assessed K+ channel responses to ACh stimulation in
isolated smooth muscle cells from the circular muscle layer of the esophageal body at 2
cm (distal) and 4 cm (proximal) sites above the lower esophageal sphincter (LES).
Western immunoblots assessed ion channel and receptor expression. ACh stimulation
produced a transient increase in outward current followed by inhibition of spontaneous
transient outward currents (STOCs). These ACh-induced currents were abolished by
blockers of large conductance Ca2+-dependent K+ channels (BKCa). Distal cells
demonstrated a greater peak current density in outward current than cells from the
proximal region, and a longer-lasting outward current increase. These responses were
abolished by atropine and the specific M3 receptor antagonist 4-DAMP, but not the M1
receptor antagonist pirenzipine or the M2 receptor antagonist methoctramine. BKCa
expression along the smooth muscle esophagus was similar, but M3 receptor expression
was greater in the distal region. Therefore ACh, can differentially activate a potassium
channel (BKCa) current along the smooth muscle esophagus. This activation probably
occurs through release of intracellular calcium via an M3 pathway, and has the potential
to modulate the timing and amplitude of peristaltic contraction along the esophagus.
