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Cardiovascular Research 2003 57(3):793-803; doi:10.1016/S0008-6363(02)00775-7
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Activation and inactivation of a non-selective cation conductance by local mechanical deformation of acutely isolated cardiac fibroblasts

Andre Kamkina,b,*, Irina Kiselevaa,b and Gerrit Isenberga

aDepartment of Physiology, Martin-Luther-University of Halle, Magdeburger Strasse 6, 06097 Halle/Saale, Germany
bInstitute of Physiology (Charité), Humboldt-University, Tucholskystrasse 2, 10117 Berlin, Germany

* Corresponding author. Tel.: +49-345-557-1886; fax: +49-345-557-4019. gerrit.isenberg{at}medizin.uni-halle.de

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 (E0) 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 µm shifted E0 from –36±7 to –17±3 mV, and to –10±2 mV. Compression by 2 or 3 µm induced a negative difference current (at –45 mV –0.06±0.02 and –0.20±0.04 nA, respectively) with a reversal potential (Erev) of approx. 0 mV. The currents were carried by Na+, K+ and Cs+ ions, and were blocked by application of 8 µM Gd3+. Stretch of 2 or 3 µm hyperpolarized E0 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 Erev close to 0 mV. Application of Gd3+ shifted E0 to potentials as negative as EK (–90±4 mV). Cell dialysis with 5 mM BAPTA (pCa 8) or 5 mM Ca2+/EGTA (pCa 6) had no influence on non-selective cation currents suggesting that Ca2+ dependent conductances are unlikely to contribute. Conclusion: Compression of the isolated cardiac fibroblast caused depolarization of the membrane by activating inward currents through a non-selective cation conductance (Gns). Stretch hyperpolarizes the fibroblast, however, not by Ca2+ activation of K+-conductance. Ion selectivity, Erev, and Gd3+-sensitivity of stretch suppressed currents suggest that stretch reduces Gns that is activated by compression.

KEYWORDS Ion transport; Stretch/m-e coupling; Vasoconstriction/dilation


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