Effect of gadolinium on stretch-induced changes in contraction and intracellularly recorded action- and afterpotentials of rat isolated atrium.

Abstract

1. Atrial arrhythmias, like atrial fibrillation and extrasystoles, are common in clinical situations when atrial pressure is increased. Although cardiac mechanoelectrical feedback has been under intensive study for many years, the mechanisms of stretch-induced arrhythmias are not known in detail. This is partly due to methodological difficulties in recording intracellular voltage during stretch stimulation. In this study we investigated the effects of gadolinium (Gd3+), a blocker of stretch-activated (SA) channels, on stretch-induced changes in rat atrial action potentials and contraction force. 2. By intracellular voltage recordings from rat isolated atria we studied the effects of Gd3+ (80 microM) on stretch-induced changes in action potentials. The stretch was induced by increasing pressure inside the atrium (1 mmHg to 7 mmHg). An elastic electrode holder that moved along the atrial tissue was used in the recordings. Thus the mechanical artifacts were eliminated and the cell-electrode contact was made more stable. To examine the influence of Gd3+ on atrial contraction we stretched the atria at different diastolic pressure levels (1 to 7 mmHg) with Gd3+ application of (80 microM) or diltiazem (5.0 microM). Contraction force was monitored by recording the pressure changes generated by the atrial contractions. 3. Our results show that: (1) atrial stretch induces delayed afterdepolarizations (DADs), increase in action potential amplitude and increase in relative conduction speed; (ii) Gd3+ blocks stretch-induced DADs and action potential changes; (iii) Gd3+ inhibits pressure-stimulated increase in the atrial contraction force, while similar inhibition is not observed with diltiazem, a blocker of L-type calcium channels. 4. This study suggests that Gd3+ inhibits stretch-induced changes in cell electrophysiology and contraction in the rat atrial cells and that the effects of gadolinium are due to rather specific block of stretch-activated ion channels with only a small effect on voltage-activated calcium channels.