HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/G1233    most recent 00310.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Muinuddin, A. Articles by Diamant, N. E. Search for Related Content PubMed PubMed Citation Articles by Muinuddin, A. Articles by Diamant, N. E.

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