title: Involvement of K(Ca2+) channels in the local abnormalities and hyperkalemia following the ischemia-reperfusion injury of rat skeletal muscle.
abstract: Patch-clamp technique was used to investigate the properties of the muscular Ca2+-activated K+ channel (K(Ca2+)) in the ischemic and ischemic-reperfused rat muscle fibers and the possible involvement of this ion channel in the reperfusion-dependent hyperkalemic state. The properties of the muscular K(Ca2+) channel were unaltered following 4 h of ischemia of the lower limbs and that the serum K+ level did not change following ischemia. In contrast, after 3 h of reperfusion an over-activation of K(Ca2+) channel was observed which was related to the increase in the number of functional channels per patch area. Currents from cation aselective channels were also routinely detected in these muscles and ion channel abnormalities similar to those observed in the ischemic-reperfused muscles were also found in the contralateral muscles. Significant hyperkalemia was observed following 3 h of reperfusion. Administration of L-NAME (10 mg.kg(-1)), a nitric-oxide synthase (NOS) inhibitor, during reperfusion prevented the increase of K(Ca2+) channel activity and the activation of the cation aselective channel. The L-NAME treatment also partially antagonised the characteristic hyperkalemia observed following reperfusion. In contrast, D-NAME (20 mg.kg(-1)), the inactive antipode on NOS enzyme administered to the rats during reperfusion failed to prevent the overactivation of the K(Ca2+) channel or the hyperkalemia. Our results indicate that overactivation of K(Ca2+) channel found in the muscles following reperfusion is either directly or indirectly related to NOS activation, and contributes to the hyperkalemia. Moreover, the discovery of abnormalities similar to those of the ischemic-reperfused muscles in the contralaterals suggests that proinflammatory molecules were released from the ischemic area, accentuating the pathological state.
authors.affiliation: Unit of Pharmacology, Dept. of Pharmacobiology, Faculty of Pharmacy, University of Bari, 70126 Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Tricarico
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capriulo
authors.forename: Diana Conte
authors.initials: DC
authors.lastname: Camerino
mesh_terms: D000818:Animals; D002412:Cations / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006947:Hyperkalemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000097:blood / Q000493:pharmacokinetics; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D002412:Cations; D004791:Enzyme Inhibitors; D024681:Potassium Channels, Calcium-Activated; D019001:Nitric Oxide Synthase; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester