Potassium channel diversity within the muscular components of the feline lower esophageal sphincter

• Published in: Canadian journal of physiology and pharmacology 2004-11, Vol.82 (11), p.1006-1017
• Main Authors: Salapatek, Anne Marie F, Ji, Junzhi, Muinuddin, Ahmad, Diamant, Nicholas E
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cats; Esophageal Sphincter, Lower - cytology; Esophageal Sphincter, Lower - physiology; Female; Fundamental and applied biological sciences. Psychology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mouth. Exocrine and endocrine salivary glands. Teeth. Esophagus; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - physiology; Potassium Channel Blockers - pharmacology; Potassium Channels - physiology; Vertebrates: digestive system
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y04-090

We hypothesized that regional differences in electrophysiological properties exist within the musculature of the feline lower esophageal sphincter (LES) and that they may potentially contribute to functional asymmetry within the LES. Freshly isolated esophageal smooth muscle cells (SMCs) from the circular muscle and sling regions within the LES were studied under a patch clamp. The resting membrane potential (RMP) of the circular SMCs was significantly more depolarized than was the RMP of the sling SMCs, resulting from a higher Na + and Cl - permeability in circular muscle than in sling muscle. Large conductance Ca 2+ -activated K + (BK Ca ) set the RMP at both levels, since specific BK Ca inhibitors caused depolarization; however, BK Ca density was greatest in the circular region. A significant portion of the outward current was due to non-BK Ca , especially in sling muscle, and likely delayed rectifier K + channels (K DR ). There was a large reduction in outward current with 4-aminopyridine (4-AP) in sling muscle, while BK Ca blockers had a limited effect on the voltage-activated outward current in sling muscle. Differences in BK Ca :K DR channel ratios were also manifest by a leftward shift in the voltage-dependent activation curve in circular cells compared to sling cells. The electrophysiological differences seen between the circular and sling muscles provide a basis for their different contributions to LES activities such as resting tone and neurotransmitter responsiveness, and in turn could impart asymmetric drug responses and provide specific therapeutic targets.Key words: esophagus, esophageal motility, gastroesophageal reflux, K Ca , K DR , LES tone.