Regional differences in cholinergic regulation of potassium current in feline esophageal circular smooth muscle.
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 Ca(2+)-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 M(3) receptor antagonist 4-DAMP but not the M(1) receptor antagonist pirenzipine or the M(2) receptor antagonist methoctramine. BK(Ca) expression along the smooth muscle esophagus was similar, but M(3) 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 M(3) pathway and has the potential to modulate the timing and amplitude of peristaltic contraction along the esophagus.
Muinuddin
Ahmad
A
Departments of Medicine, University of Toronto, Toronto, Ontario, Canada.
Naqvi
Khurram
K
Sheu
Laura
L
Gaisano
Herbert Y
HY
Diamant
Nicholas E
NE
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004594:Electrophysiology; D004947:Esophagus / Q000033:anatomy & histology / Q000502:physiology*; D008564:Membrane Potentials; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000502:physiology*
D018727:Muscarinic Antagonists; D010880:Piperidines; D015221:Potassium Channels; D043587:Receptor, Muscarinic M3; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D000109:Acetylcholine