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NEUROREGULATION AND MOTILITY

Regional differences in cholinergic regulation of potassium current in feline esophageal circular smooth muscle

Departments of ¹Medicine and ²Physiology, University of Toronto, and ³Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada

Submitted 13 July 2004 ; accepted in final form 26 January 2005

Potassium channels are important contributors to membrane excitability in smooth muscles. There are regional differences in resting membrane potential 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 (distal)- and 4-cm (proximal) sites above the lower esophageal sphincter. 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. These ACh-induced currents were abolished by blockers of large-conductance Ca²⁺-dependent K⁺ channels (BK_Ca). 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. BK_Ca 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 (BK_Ca) 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.

esophagus; acetylcholine; potassium channel