Mechanically induced potentials in atrial fibroblasts from rat hearts are sensitive to hypoxia/reoxygenation

Abstract

Membrane potential changes of atrial fibroblasts in response to mechanical stress have been considered to modulate the rhythmic electrical activity of healthy hearts. Our recent findings suggest that cardiac arrhythmia after infarction is related to enhanced susceptibility of the fibroblasts to physical stretch. In this study, we analysed the effect of hypoxia/reoxygenation, which are major components of tissue ischemia/reperfusion, on the membrane potential of atrial fibroblasts. Intracellular microelectrode recordings were performed together with isometric force measurements on isometrically contracting right atrial tissue preparations from adult rats. Lowering the oxygen tension in the perfusate from 80 kPa to 3.5 kPa reduced active force development and decreased the resting membrane potential of the cardiac fibroblasts from -23+/-5 mV to -5+/-2 mV ( n=35). Application of gadolinium (40 microM) to inhibit non-selective cation channels prevented hypoxia-induced membrane depolarization of the fibroblasts. Reoxygenation of the myocardial tissue resulted in a transient increase of the resting membrane potential to maximally -60+/-8 mV. These findings indicate that transmembrane currents in atrial fibroblasts are sensitive to changes in tissue oxygenation. In conclusion, altered electro-mechanical function of the ischemic heart may possibly involve changes of the membrane potential of the cardiac fibroblasts.

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

“…This current reversed at about −20 mV, which coincided with the resting potentials of the control fibroblasts and of those exposed to hypoxia, and also with those reported previously in rat cardiac fibroblasts (12). The reversal potential of −20 mV suggested a possibility of Cl − channels or a nonselective cation channel.…”

2011 ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

“…Other factors potentially involved in the induction or maintenance of AF include inflammation, autonomic nervous system activity, atrial ischemia, 154 atrial dilation, 155 anisotropic conduction, 156 and structural changes associated with aging. 3 It has been postulated that oxidative stress and inflammation may be involved in the genesis of AF.…”

A review of the literature on cardiac electrical activity between fibroblasts and myocytes

“…Recently, it was reported that rat ventricular fibroblasts possess an inward rectifier K+ current (I Kir ) and a delayed rectifier K+ current (I Kr )(Chilton et al, 2005; Rose et al, 2007; Shibukawa et al, 2005). In addition, human cardiac fibroblasts were shown to express calcium-activated big conductance potassium channels (BK Ca )(Wang et al, 2006), as well as additional nonselective channels (Du et al, 2010; El Chemaly et al, 2006; Kamkin et al, 2003a; Kamkin et al, 2005; Kamkin et al, 2003b; Ma et al, 2008; Rose et al, 2007). In addition, recent studies have indicated fibroblasts isolated from normal hearts and maintained in culture express ATP-sensitive K+ channel (K ATP ) subunits (Benamer et al, 2013; Chilton et al, 2005).…”