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 MOmega. At intracellular pCa 7 (patch-pipette solution), compression of 2 or 3 mum shifted E,) from -36+/-7 to -17+/-3 mV, and to -10+/-2 mV. Compression by 2 or 3 Rut induced a negative difference current (at -45 mV -0.06+/-0.02 and -0.20+/-0.04 nA, respectively) with a reversal potential (E,,v) of approx. 0 mV. The currents were carried by Na+, K+ and Cs+ ions, and were blocked by application of 8 muM Gd3+. Stretch of 2 or 3 mum hyperpolarized E-0 from -34+/-4 to -45+/-5, and to -61+/-7 mV and induced a positive difference current (at -45 mV: 0.041+/-0.02 and 0.18+/-0.03 nA) with an E-rev close to 0 mV. Application of Gd3+ shifted E-0 to potentials as negative as E-k (-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 (G(ns)). Stretch hyperpolarizes the libroblast, however, not by Ca2+ activation of K+-conductance. Ion selectivity, E-rev, and Gd3+-sensitivity of stretch suppressed currents suggest that stretch reduces G(ns) that is activated by compression. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.