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

When atrial tissue contracts, mechanically induced potentials (MIPs) are ge nerated in fibroblasts, presumably by activation of a non-selective cation conductance G(ns). Non-stimulated atrial fibroblasts had a mean ( SD) membr ane potential (Em) of -22 +/-2 mV and an input resistance of 510 +/- 10 M O mega. MIP amplitude (A(MIP)) was 38 +/-4 mV when current injection had pola rised E-m to Vm=-50 mV. The slope of the function relating A(MIP) to Vm can be regarded as a mechanosensitive factor (X-ms) that describes the relativ e increase in Gls during a MIR Putative involvement of cytoskeletal fibres in activation of G(ns) was studied by delivering drugs from the intracellul ar recording, microelectrode. Destabilisation of F-actin by 0.2 mM cytochal asin D reduced A(MIP) from 38 to 16 mV and X-ms from 5 to 1.8. Destabilisat ion 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 a nd X-ms to 1.4. Promoting F-actin stability with exogenous adenosine 5 ' -t riphosphate (ATP) increased A(MIP) and X-ms and attenuated the effects of c ytochalasin D. Similarly, facilitation of tubulin stability with guanosine 5 ' -triphosphate (GTP) or taxol increased A(MIP) and X-ms and attenuated t he effects of colchicine. The results suggest that transfer of mechanical e nergy from the deformed fibroblast surface to the G(ns) channel protein dep ends on intact F-actin and tubulin fibres.