Intracellular redistribution of dihydropyridine receptor in the rat heart during the progression of sepsis.
BACKGROUND
Dihydropyridine receptor (DHPR) regulates the rate and force of cardiac muscle contraction. This study examined the alteration in the intracellular redistribution of DHPR and its association with the development of the two distinct cardiodynamic states in the rat heart during the progression of sepsis.


METHODS
Sepsis was induced by cecal ligation and puncture (CLP). DHPRs were assayed using [(3)H]PN200-100 binding and photoaffinity labeling with [(3)H]azidopine followed by polyacrylamide gel electrophoresis.


RESULTS
[(3)H]PN200-110 binding shows that during the early hyperdynamic phase of sepsis (9 h post-CLP), the Bmax was increased by 27% in sarcolemma while decreased by 24% in light vesicle. During the late hypodynamic phase of sepsis (18 h post-CLP), the Bmax was decreased by 39% in sarcolemma but increased by 59% in light vesicle. The sum of the Bmax for both membrane fractions was increased by 16% during early sepsis while decreased by 17% during late sepsis. Photoaffinity labeling shows that the incorporation of [(3)H]azidopine into 165 kDa peptides during early sepsis was increased by 28% in sarcolemma whereas decreased by 23% in light vesicle. During late sepsis, the incorporation was decreased by 38% in sarcolemma but increased by 46% in light vesicle. The sum of the 165 kDa peptides for both membrane fractions was increased by 13% during early while decreased by 13% during late sepsis.


CONCLUSIONS
These data indicate that DHPRs in the rat heart were externalized from light vesicles to sarcolemma during the early hyperdynamic phase whereas they were internalized from surface membranes to intracellular sites during the late hypodynamic phase of sepsis. Furthermore, DHPRs were overexpressed during early sepsis while they were underexpressed during late sepsis. Alterations in the expression and intracellular redistribution of DHPRs may contribute to the development of the biphasic cardiodynamic states during the progression of sepsis.
Hsu
Chin
C
Department of Physiology, Graduate Institute of Physiology and Molecular Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wu
Guang
G
Yang
Shaw-Lang
SL
Hsu
Hseng-Kuang
HK
Yang
Rei-Cheng
RC
Tang
Chaoshu
C
Liu
Maw-Shung
MS
D000818:Animals; D020746:Calcium Channels, L-Type / Q000032:analysis* / Q000378:metabolism; D018450:Disease Progression; D017275:Isradipine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism*
D020746:Calcium Channels, L-Type; D011943:Receptors, Adrenergic, beta; D017275:Isradipine