Dietary cholesterol alters Na+/K+ selectivity at intracellular Na+/K+ pump sites in cardiac myocytes.
Am J Physiol Cell Physiol
; 286(2): C398-405, 2004 Feb.
Article
em En
| MEDLINE
| ID: mdl-14522815
ABSTRACT
A modest diet-induced increase in serum cholesterol in rabbits increases the sensitivity of the sarcolemmal Na+/K+ pump to intracellular Na+, whereas a large increase in cholesterol levels decreases the sensitivity to Na+. To examine the mechanisms, we isolated cardiac myocytes from controls and from rabbits with diet-induced increases in serum cholesterol. The myocytes were voltage clamped with the use of patch pipettes that contained osmotically balanced solutions with Na+ in a concentration of 10 mM and K+ in concentrations ([K+]pip) ranging from 0 to 140 mM. There was no effect of dietary cholesterol on electrogenic Na+/K+ current (Ip) when pipette solutions were K+ free. A modest increase in serum cholesterol caused a [K+]pip-dependent increase in Ip, whereas a large increase caused a [K+]pip-dependent decrease in Ip. Modeling suggested that pump stimulation with a modest increase in serum cholesterol can be explained by a decrease in the microscopic association constant KK describing the backward reaction E1 + 2K+ --> E2(K+)2, whereas pump inhibition with a large increase in serum cholesterol can be explained by an increase in KK. Because hypercholesterolemia upregulates angiotensin II receptors and because angiotensin II regulates the Na+/K+ pump in cardiac myocytes in a [K+]pip-dependent manner, we blocked angiotensin synthesis or angiotensin II receptors in vivo in cholesterol-fed rabbits. This abolished cholesterol-induced pump inhibition. Because the epsilon-isoform of protein kinase C (epsilonPKC) mediates effects of angiotensin II on the pump, we included specific epsilonPKC-blocking peptide in patch pipette filling solutions. The peptide reversed cholesterol-induced pump inhibition.
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Bases de dados:
MEDLINE
Assunto principal:
Potássio
/
Sódio
/
Colesterol na Dieta
/
ATPase Trocadora de Sódio-Potássio
/
Miócitos Cardíacos
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Austrália