Patch-clamp technique was used to investigate the proper-ties of the muscular Ca2+-activated K+ channel (KCa2+) 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 KCa2+ 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 KCa2+ 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 KCa2+ 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 KCa2+ channel or the hyperkalemia. Our results indicate that overactivation of KCa2+ 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.

Involvement of K(Ca2+)channels in the local abnormalities and hyperkalemia following the ischemia-reperfusion injury of rat skeletal muscle

TRICARICO, Domenico;CONTE, Diana
2002

Abstract

Patch-clamp technique was used to investigate the proper-ties of the muscular Ca2+-activated K+ channel (KCa2+) 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 KCa2+ 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 KCa2+ 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 KCa2+ 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 KCa2+ channel or the hyperkalemia. Our results indicate that overactivation of KCa2+ 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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/136196
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 25
social impact