Lysophosphatidyl choline modulates mechanosensitive L-type Ca2+ current in circular smooth muscle cells from human jejunum.
The L-type Ca2+ channel expressed in gastrointestinal smooth muscle is mechanosensitive. Direct membrane stretch and shear stress result in increased Ca2+ entry into the cell. The mechanism for mechanosensitivity is not known, and mechanosensitivity is not dependent on an intact cytoskeleton. The aim of this study was to determine whether L-type Ca2+ channel mechanosensitivity is dependent on tension in the lipid bilayer in human jejunal circular layer myocytes. Whole cell currents were recorded in the amphotericin-perforated-patch configuration, and lysophosphatidyl choline (LPC), lysophosphatidic acid (LPA), and choline were used to alter differentially the tension in the lipid bilayer. Shear stress (perfusion at 10 ml/min) was used to mechanostimulate L-type Ca2+ channels. The increase in L-type Ca2+ current induced by shear stress was greater in the presence of LPC (large head-to-tail proportions), but not LPA or choline, than in the control perfusion. The increased peak Ca2+ current also did not return to baseline levels as in control conditions. Furthermore, steady-state inactivation kinetics were altered in the presence of LPC, leading to a change in window current. These findings suggest that changes in tension in the plasmalemmal membrane can be transmitted to the mechanosensitive L-type Ca2+ channel, leading to altered activity and Ca2+ entry in the human jejunal circular layer myocyte.
Kraichely
Robert E
RE
Enteric Neuroscience Program, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
Strege
Peter R
PR
Sarr
Michael G
MG
Kendrick
Michael L
ML
Farrugia
Gianrico
G
D000200:Action Potentials; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D006801:Humans; D007583:Jejunum / Q000166:cytology*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008246:Lysophospholipids / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008958:Models, Molecular; D032389:Myocytes, Smooth Muscle / Q000502:physiology*
D020746:Calcium Channels, L-Type; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; C032881:lysophosphatidic acid