BACKGROUND & AIMS: Sodium channels are key regulators of neuronal and muscle excitability. However, sodium channels have not been definitively identified in gastrointestinal smooth muscle. The aim of the present study was to determine if a Na(+) current is present in human jejunal circular smooth muscle cells. METHODS: Currents were recorded from freshly dissociated cells using patch-clamp techniques. Complementary DNA (cDNA) libraries constructed from the dissociated cells were screened to determine if a message for alpha subunits of Na(+) channels was expressed. Smooth muscle cells were also collected using laser-capture microdissection and screened. RESULTS: A tetrodotoxin-insensitive Na(+) channel was present in 80% of cells patch-clamped. Initial activation was at -65 mV with peak inward current at -30 mV. Steady-state inactivation and activation curves revealed a window current between -75 and -60 mV. The Na(+) current was blocked by lidocaine and internal and external QX314. A cDNA highly homologous to SCN5A, the alpha subunit of the cardiac Na(+) channel, was present in the cDNA libraries constructed from dissociated cells and from smooth muscle cells collected using laser-capture microdissection. CONCLUSIONS: Human jejunal circular smooth muscle cells express a tetrodotoxin-insensitive Na(+) channel, probably SCN5A. Whether SCN5A plays a role in the pathophysiology of human gut dysmotilities remains to be determined.
BACKGROUND & AIMS:Sodium channels are key regulators of neuronal and muscle excitability. However, sodium channels have not been definitively identified in gastrointestinal smooth muscle. The aim of the present study was to determine if a Na(+) current is present in human jejunal circular smooth muscle cells. METHODS: Currents were recorded from freshly dissociated cells using patch-clamp techniques. Complementary DNA (cDNA) libraries constructed from the dissociated cells were screened to determine if a message for alpha subunits of Na(+) channels was expressed. Smooth muscle cells were also collected using laser-capture microdissection and screened. RESULTS: A tetrodotoxin-insensitive Na(+) channel was present in 80% of cells patch-clamped. Initial activation was at -65 mV with peak inward current at -30 mV. Steady-state inactivation and activation curves revealed a window current between -75 and -60 mV. The Na(+) current was blocked by lidocaine and internal and external QX314. A cDNA highly homologous to SCN5A, the alpha subunit of the cardiac Na(+) channel, was present in the cDNA libraries constructed from dissociated cells and from smooth muscle cells collected using laser-capture microdissection. CONCLUSIONS:Human jejunal circular smooth muscle cells express a tetrodotoxin-insensitive Na(+) channel, probably SCN5A. Whether SCN5A plays a role in the pathophysiology of human gut dysmotilities remains to be determined.
Authors: Leila Neshatian; Peter R Strege; Poong-Lyul Rhee; Robert E Kraichely; Amelia Mazzone; Cheryl E Bernard; Robert R Cima; David W Larson; Eric J Dozois; Crystal F Kline; Peter J Mohler; Arthur Beyder; Gianrico Farrugia Journal: Am J Physiol Gastrointest Liver Physiol Date: 2015-07-16 Impact factor: 4.052
Authors: Arthur Beyder; Amelia Mazzone; Peter R Strege; David J Tester; Yuri A Saito; Cheryl E Bernard; Felicity T Enders; Weronica E Ek; Peter T Schmidt; Aldona Dlugosz; Greger Lindberg; Pontus Karling; Bodil Ohlsson; Maria Gazouli; Gerardo Nardone; Rosario Cuomo; Paolo Usai-Satta; Francesca Galeazzi; Matteo Neri; Piero Portincasa; Massimo Bellini; Giovanni Barbara; Michael Camilleri; G Richard Locke; Nicholas J Talley; Mauro D'Amato; Michael J Ackerman; Gianrico Farrugia Journal: Gastroenterology Date: 2014-03-05 Impact factor: 22.682
Authors: Andelain Erickson; Annemie Deiteren; Andrea M Harrington; Sonia Garcia-Caraballo; Joel Castro; Ashlee Caldwell; Luke Grundy; Stuart M Brierley Journal: J Physiol Date: 2018-02-06 Impact factor: 5.182
Authors: Robert E Kraichely; Peter R Strege; Michael G Sarr; Michael L Kendrick; Gianrico Farrugia Journal: Am J Physiol Gastrointest Liver Physiol Date: 2009-01-29 Impact factor: 4.052