STRETCH-ACTIVATED CHANNEL BLOCKERS MODULATE CELL-VOLUME IN CARDIAC VENTRICULAR MYOCYTES

Stretch-activated channels (SAC) are postulated to regulate cell volum e. While this hypothesis is appealing, direct evidence is lacking. Usi ng digital video microscopy, we found that pharmacological blockade of SACs alters the cell volume of isolated rabbit ventricular myocytes d uring hypoosmotic stress, Under control conditions, relative cell volu me increased from 1.0 to 1.311 +/- 0.019 after 10 min in 195 mosmol/l solution, The cation SAC blocker gadolinium (Gd3+; 10 mu M) reduced th e amount of swelling in hypoosmotic solution by 24% and induced a regu latory volume decrease otherwise not observed, In contrast, the anion SAC blocker 9-anthracene carboxylic acid (9-AC; 1 mM) increased swelli ng by 44% under the same conditions, Based on the direction of SAC cur rents, Gd3+ and 9-AC are expected to have opposite effects on cell vol ume. Furthermore, Gd3+ and 9-AC changed cell volume by only similar to 2% in isosmotic solutions when SACs are expected to be closed. This s upports the idea that Gd3+ and 9-AC affect stretch-activated transport processes, In contrast, omitting bath Ca2+ did not alter cell volume under iso- or hypoosmotic conditions suggesting stretch-activated Ca2 influx is not important in setting cell volume, Not all channels can affect cell volume. Opening ATP-sensitive K+ channels with aprikalim ( 100 mu M) or blocking them with glibenclamide (1 mu M) did not alter c ell volume under isosmotic or hypoosmotic conditions, These data suppo rt the idea that SACs are involved in cardiac cell volume regulation.