Activation and inactivation of a non-selective cation conductance by local mechanical deformation of acutely isolated cardiac fibroblasts.
OBJECTIVE
We describe mechanically induced non-selective cation currents in isolated rat atrial fibroblasts, which might play a role as a substrate for mechano-electrical feedback in the heart.


METHODS
Isolated fibroblasts were used for voltage-clamp analysis of ionic currents generating mechanically-induced potentials. Fibroblasts were mechanically deformed (compressed or stretched) by two patch-pipettes.


RESULTS
These cells had a resting potential (E(0)) of -37+/-3 mV and an input resistance of 514+/-11 M(Omega). At intracellular pCa 7 (patch-pipette solution), compression of 2 or 3 microm shifted E(0) from -36+/-7 to -17+/-3 mV, and to -10+/-2 mV. Compression by 2 or 3 microm induced a negative difference current (at -45 mV -0.06+/-0.02 and -0.20+/-0.04 nA, respectively) with a reversal potential (E(rev)) of approx. 0 mV. The currents were carried by Na(+), K(+) and Cs(+) ions, and were blocked by application of 8 microM Gd(3+). Stretch of 2 or 3 microm hyperpolarized E(0) from -34+/-4 to -45+/-5, and to -61+/-7 mV and induced a positive difference current (at -45 mV: 0.04+/-0.02 and 0.18+/-0.03 nA) with an E(rev) close to 0 mV. Application of Gd(3+) shifted E(0) to potentials as negative as E(K) (-90+/-4 mV). Cell dialysis with 5 mM BAPTA (pCa 8) or 5 mM Ca(2+)/EGTA (pCa 6) had no influence on non-selective cation currents suggesting that Ca(2+) dependent conductances are unlikely to contribute.


CONCLUSIONS
Compression of the isolated cardiac fibroblast caused depolarization of the membrane by activating inward currents through a non-selective cation conductance (G(ns)). Stretch hyperpolarizes the fibroblast, however, not by Ca(2+) activation of K(+)-conductance. Ion selectivity, E(rev,) and Gd(3+)-sensitivity of stretch suppressed currents suggest that stretch reduces G(ns) that is activated by compression.
Kamkin
Andre
A
Department of Physiology, Martin-Luther-University of Halle, Magdeburger Strasse 6, 06097 Halle/Saale, Germany. gerrit.isenberg@medizin.uni-halle.de
Kiseleva
Irina
I
Isenberg
Gerrit
G
D000818:Animals; D002478:Cells, Cultured; D004151:Dipeptides; D004594:Electrophysiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D051381:Rats
D004151:Dipeptides; D024681:Potassium Channels, Calcium-Activated; C068249:N-(3-ethoxycarbonyloxirane-2-carbonyl)-isoleucyl-proline