ATP-sensitive potassium channels (K(ATP)) in retina: a key role for delayed ischemic tolerance.
The objectives of the present study were to determine the localization of K(ATP) channels in normal retina and to evaluate their potential roles in ischemic preconditioning (IPC) in a rat model of ischemia induced by increased intraocular pressure (IOP). Brown Norway rats were subjected to sublethal 3-, lethal 20- and 40-min ischemia and the functional recovery was evaluated using electroretinography. The time interval between ischemic insults ranged from 1 to 72 h. The effects of K(ATP) channel blockade on IPC protection were studied by treatment with 0.01% glipizide. IPC was mimicked by injection of K(ATP) channel openers of 0.01% (-)cromakalim or 0.01% P1060 72 h before 20-min ischemia. Co-expression of K(ATP) channel subunits Kir6.2/SUR1 was observed in the retinal pigment epithelium, inner segments of photoreceptors, outer plexiform and ganglion cell layers and at the border of the inner nuclear layer. In contrast to a 20- or 40-min ischemia, a 3-min ischemia induced no alteration of the electroretinogram (ERG) and constituted the preconditioning stimulus. An ischemic challenge of 40 min in preconditioned rats induced impairment of retinal function. However, animals preconditioned 24, 48 and 72 h before 20-min ischemia had a significant improvement of the ERG. (-)Cromakalim and P1060 mimicked the effect of IPC. Glipizide significantly suppressed the protective effects of preconditioning. In conclusion, activation of K(ATP) channels plays an important role in the mechanism of preconditioning by enhancing the resistance of the retina against a severe ischemic insult.
Ettaiche
M
M
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Heurteaux
C
C
Blondeau
N
N
Borsotto
M
M
Tinel
N
N
Lazdunski
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D015870:Gene Expression / Q000502:physiology; D005913:Glipizide; D007004:Hypoglycemic Agents; D017403:In Situ Hybridization; D007429:Intraocular Pressure; D007511:Ischemia / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000378:metabolism*
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D005913:Glipizide