Mechanically induced potentials in rat atrial fibroblasts depend on actin and tubulin polymerisation

Abstract.

When atrial tissue contracts, mechanically induced potentials (MIPs) are generated in fibroblasts, presumably by activation of a non-selective cation conductance G _ns. Non-stimulated atrial fibroblasts had a mean (±SD) membrane potential (E _m) of –22±2 mV and an input resistance of 510±10 MΩ. MIP amplitude (A _MIP) was 38±4 mV when current injection had polarised E _m to V _m=–50 mV. The slope of the function relating A _MIP to V _m can be regarded as a mechanosensitive factor (X _ms) that describes the relative increase in G _ns during a MIP. Putative involvement of cytoskeletal fibres in activation of G _ns was studied by delivering drugs from the intracellular recording microelectrode. Destabilisation of F-actin by 0.2 mM cytochalasin D reduced A _MIP from 38 to 16 mV and X _ms from 5 to 1.8. Destabilisation of tubulin with 0.2 mM colchicine reduced A _MIP to 21 mV and X _ms to 2.1. The combination colchicine plus cytochalasin D reduced A _MIP to 9 mV and X _ms to 1.4. Promoting F-actin stability with exogenous adenosine 5′-triphosphate (ATP) increased A _MIP and X _ms and attenuated the effects of cytochalasin D. Similarly, facilitation of tubulin stability with guanosine 5′-triphosphate (GTP) or taxol increased A _MIP and X _ms and attenuated the effects of colchicine. The results suggest that transfer of mechanical energy from the deformed fibroblast surface to the G _ns channel protein depends on intact F-actin and tubulin fibres.