Mechanosensitive Ion Channels

Introductory Work in Mechanosensitive Calcium and Potassium Channels
Mechanosensitive Sodium Channel
Mechanosensitive Calcium Channel
Relevant Pharmacology of Sodium, Calcium, and Potassium Channels

Mechanosensitive ion channels are ion channels whose gating can be altered by mechanical forces. Mechanical stress is subsequently transformed into an electrical response. A recent interest of the laboratory has been the study of mechanosensitive ion channels in human jejunal circular smooth muscle cells. The cells appear to express a mechanosensitive L-type calcium channel. The presence of mechanosensitive ion channels in gastrointestinal smooth muscle suggests that gastrointestinal smooth muscle is not only a motor organ but also a sensory organ, able to sense and directly respond to changes in its environment. Here is a video clip describing the relationship between a mechanosensitive calcium channel (BLUE), BK (large conductance, calcium activated potassium channel, GREEN), and the cell contractile state. As perfusion mechanically stimulates the MS Ca2+ channel, calcium begins to enter the cell. Calcium concentration increases (indicated by red color), the cell contracts and BK channels activate. This allows K+ to leave the cell, hyperpolarizing the cell, and leads to cell relaxation.

Selected Publications (Click here for complete list of publications)

• Strege PR, Bernard CE, Ou Y, Gibbons SJ, Farrugia G. Effect of mibefradil on sodium and calcium currents. Am J Physiol Gastrointest Liver Physiol. 2005 Aug;289(2):G249-53. Epub 2005 Mar 24.
• Lim I, Gibbons SJ, Lyford GL, Miller SM, Strege PR, Sarr MG, Chatterjee S, Szurszewski JH, Shah VH, Farrugia G. Carbon monoxide activates human intestinal smooth muscle L-type Ca2+ channels through a nitric oxide-dependent mechanism. Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G7-G14.
• Strege PR, Evangelista S, Lyford GL, Sarr MG, Farrugia G. Otilonium bromide inhibits calcium entry through L-type calcium channels in human intestinal smooth muscle. Neurogastroenterol Motil. 2004 Apr;16(2):167-73.
• Lyford GL, Farrugia G. Ion channels in gastrointestinal smooth muscle and interstitial cells of Cajal. Curr Opin Pharmacol. 2003 Dec;3(6):583-7.
• Strege PR, Ou Y, Sha L, Rich A, Gibbons SJ, Szurszewski JH, Sarr MG, Farrugia G. Sodium current in human intestinal interstitial cells of Cajal. Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1111-21. Epub 2003 Jul 31.
• Strege PR, Holm AN, Rich A, Miller SM, Ou Y, Sarr MG, Farrugia G. Cytoskeletal modulation of sodium current in human jejunal circular smooth muscle cells. Am J Physiol Cell Physiol. 2003 Jan;284(1):C60-6.
• Ou Y, Strege PR, Miller SM, Makielski J, Ackerman MJ, Gibbons SJ, Farruiga G. Syntrophin gamma 2 regulates SCN5A gating by a PDZ domain-mediated interaction. J Biol Chem 2003 Jan 17;278(3):1915-1923.
• Malysz J, Farrugia G, Ou Y, Szurszewski JH, Nehra A, Gibbons SJ. The Kv2.2 alpha subunit contributes to delayed rectifier K(+) currents in myocytes from rabbit corpus cavernosum. J Androl. 2002 Nov-Dec;23(6):899-910.
• Ou Y, Gibbons SJ, Miller SM, Strege PR, Rich A, Distad MA, Ackerman MJ, Rae JL, Szurszewski JH, Farrugia G. SCN5A is expressed in Human Jejunal Circular Smooth Muscle Cells. Neurogastroenterol Motil. 2002 Oct;14(5):477-486.
• Lyford GL, Strege PR, Shepard A, Ou Y, Ermilov L, Miller SM, Gibbons SM, Rae JL, Szurszewski JH, Farrugia G. alpha1C (CaV1.2) L-type calcium channel mediates mechanosensitive calcium regulation. Am J Physiol Cell Physiol 2002 Sep;283(3):C1001-8.
• Holm AN, Rich A, Miller SM, Strege P, Ou Y, Gibbons S, Sarr MG, Szurszewski JH, Rae JL, Farrugia G. Sodium current in human jejunal circular smooth muscle cells. Gastroenterology. 2002 Jan;122(1):178-87.
• Holm AN, Rich A, Sarr MG, Farrugia G. Whole cell current and membrane potential regulation by a human smooth muscle mechanosensitive calcium channel. Am J Physiol Gastrointest Liver Physiol 2000 Dec;279(6):G1155-61
• Farrugia G, Holm AN, Rich A, Sarr MG, Rae JL, Szurszewski JH. (1999). A mechanosensitive calcium channel in human intestinal smooth muscle cells. Gastroenterology. 117:900-905.
• Farrugia G, et al. (1993). Effect of volume changes on a potassium current in rabbit corneal epithelial cells. Am J Physiol. 264(5 Pt 1):C1238-45.
• Farrugia G, Rich A, Rae JL, Sarr MG, Szurszewski JH. (1995). Calcium currents in human and canine jejunal circular smooth muscle cells. Gastroenterology. 109:707-717.