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Gastroenterology. 2001 Nov;121(5):1209-18.

Altered cellular calcium regulatory systems in a rat model of cirrhotic cardiomyopathy.

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1
Department of Physiology, Queen's University, Kingston, Ontario, Canada.

Abstract

BACKGROUND & AIMS:

Decreased cardiac contractility has been observed in cirrhosis, but the cause remains unclear. Because cardiomyocyte contraction depends on Ca2+ influx entering via L-type Ca2+ channels (I(Ca,L)s) to activate Ca2+ release from the sarcoplasmic reticulum, we postulated that the Ca2+ transients may be abnormal in cirrhotic cardiomyocytes. We aimed to investigate the status of the cellular Ca2+-regulatory system in a rat model of cirrhotic cardiomyopathy.

METHODS:

Cirrhosis was induced by bile duct ligation. The I(Ca,L) protein expression was detected by Western blotting. Ca2+ currents were measured electrophysiologically. The intracellular Ca2+ system, which includes the ryanodine receptor 2 (RYR2), sarcoplasmic reticulum Ca2+-pump adenosine triphosphatase (SERCA2), and Ca2+-binding protein were quantitatively assayed by reverse-transcription polymerase chain reaction and Western blots and functionally by 3H-ryanodine binding and radiolabeled Ca2+ uptake.

RESULTS:

I(Ca,L) protein expression was reduced in cirrhotic rats compared with controls, and the peak inward Ca2+ current was significantly less. At all membrane potentials examined, I(Ca,L)s current densities from cirrhotic animals were consistently lower, and the response to maximal isoproterenol stimulation was also significantly lower. Protein expression and messenger RNA transcription for RYR2, SERCA2, and calsequestrin were quantitatively unchanged, and 3H-ryanodine binding characteristics and Ca2+ uptake were also unaltered.

CONCLUSIONS:

We conclude that the decreased cardiac contractility in cirrhotic cardiomyocytes is caused by dysfunction of the Ca2+-regulatory system. Plasma membrane I(Ca,L)s are quantitatively reduced and functionally depressed, whereas intracellular systems are intact.

PMID:
11677214
[Indexed for MEDLINE]
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