Mechanical deformation of ventricular myocytes modulates both TRPC6 and Kir2.3 channels.
Cardiomyocytes respond to mechanical stretch with an increase [Ca2+]i. Here, we analyzed which ion channels could mediate this effect. Murine ventricular myocytes were attached to a glass coverslip and a cell-attached glass stylus sheared the upper cell part versus the attached cell bottom. At negative clamp potentials, stretch induced inward currents that increased with the extent of stretch and reversed within 2 min after relaxation from stretch. Stretch activated a nearly voltage-independent GsMTx-4-sensitive non-selective cation conductance Gns, antibodies against TRPC6 prevented Gns activation. In addition, stretch deactivated a Cs+-sensitive inwardly rectifying potassium conductance GK1, antibodies against Kir2.3 inhibited this effect. Immunolabeling localized TRPC6 and Kir2.3 in T-tubular membranes, and stretch-induced changes in membrane currents were absent in cells whose T-tubules had been removed. In absence of stretch, we could activate Gns and deactivate GK1 by 1-oleoyl-2-acetyl-sn-glycerol (OAG) and other amphipaths. We interpret that the function of TRPC6 and Kir2.3 channels is controlled by both tension and curvature of the surrounding lipid bilayer that are changed by incorporation of amphipaths. Stretch-activation of TRPC6 channels may increase Ca2+ influx directly and indirectly, by membrane depolarization (activation of voltage-gated Ca2+ channels) and by elevated [Na+]i (augmented Na+,Ca2+-exchange).
Dyachenko
V
V
Department of Physiology, Martin-Luther-University Halle, 06097 Halle, Germany.
Husse
B
B
Rueckschloss
U
U
Isenberg
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D021381:Protein Transport; D013314:Stress, Mechanical; D050052:TRPC Cation Channels / Q000502:physiology*; D000074287:TRPC6 Cation Channel
C490969:Kcnj4 protein, mouse; D024661:Potassium Channels, Inwardly Rectifying; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; D002118:Calcium