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 (E₀) of −37±3 mV and an input resistance of 514±11 MΩ. 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 (E_rev) 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 E_rev close to 0 mV. Application of Gd³⁺ shifted E₀ 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 fibroblast, 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.