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NEUROREGULATION AND MOTILITY

Regional differences in L-type Ca²⁺ channel expression in feline lower esophageal sphincter

Departments of ¹Medicine and ²Physiology, University of Toronto, Toronto, Ontario M5S 1A8; and ³Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada M5T 2S8

Submitted 7 March 2004 ; accepted in final form 27 May 2004

In humans and cats, muscle from the lower esophageal sphincter (LES) circular region exhibits greater spontaneous tone than LES sling muscle, whereas the sling muscle is much more responsive to cholinergic stimulation. Despite physiological and pharmacological evidence for the presence of L-type Ca²⁺ channel current (I_Ca,L) activity in LES circular muscle, the identity of this channel has not been demonstrated biochemically or electrophysiologically fingerprinted. Furthermore, there is no information on the channel's presence and role in the sling region of the LES. We hypothesized that regional differences in the expression of I_Ca,L between LES circular and sling muscles, if present, could contribute to the functional asymmetry observed within the LES. I_Ca,L expression was compared between circular and sling regions of the LES by Western blot analysis. The patch-clamp technique was used to study I_Ca,L. Muscle strip studies assessed I_Ca,L contribution to contractile activity. We found both protein expression of I_Ca,L and I_Ca,L density to be greater in LES circular muscle than sling muscle. I_Ca,L voltage- and time-dependent activation and inactivation curves were similar in cells from both regions. I_Ca,L blockade with nifedipine inhibited spontaneous tone and ACh-induced contractions only in circular muscle but was able to abolish depolarization (KCl)-induced contractions in both sling and circular muscles. In contrast, La³⁺ inhibited tone and ACh-induced contractions in muscles from both regions. Therefore, regional myogenic differences in I_Ca,L expression within the LES circular and sling muscle exist and provide one explanation for the differential contribution of sling and circular muscle to LES contractility.

lower esophageal sphincter; sling; smooth muscle

This article has been cited by other articles:

				M.-C. L'Heureux, A. Muinuddin, H. Y. Gaisano, and N. E. Diamant Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G23 - G29. [Abstract] [Full Text] [PDF]

				J. R. Kovac, H. G. Preiksaitis, and S. M. Sims Functional and molecular analysis of L-type calcium channels in human esophagus and lower esophageal sphincter smooth muscle Am J Physiol Gastrointest Liver Physiol, December 1, 2005; 289(6): G998 - G1006. [Abstract] [Full Text] [PDF]