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Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure.

Abstract：

OBJECTIVE:Myocardial cellular electrophysiology and intracellular Ca2+ regulation are altered in heart failure. The extent of these changes may vary within the layers of the ventricular wall. To examine this, cell size, action potential and intracellular Ca2+ transient characteristics (Fura-2) were measured in single cardiac myocytes from sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricle of rabbits with heart failure. METHODS:Myocytes were isolated from animals with heart failure induced by chronic coronary artery ligation and from sham operated controls. Trans-membrane potential was measured using high resistance microelectrodes electrodes (30 M omega; 2 M KC1). Fura-2 was loaded into cells by incubation with the AM form. Subsequent fluorescence measurements were used to measure intracellular Ca2+ concentration at a range of stimulus frequencies. RESULTS:Resting cell length was significantly greater in the heart failure group; approximately 115% of control values in sub-epicardial and mid-myocardial cells, and approximately 108% in sub-endocardial cells. Using criteria described by previous studies on other mammalian hearts, functional M cells were identified by a higher maximum rate of depolarisation and longer action potential duration at 90% repolarisation (APD90) compared to the two other myocyte sub-types. In the heart failure group, APD90 and Ca2+ transient duration (CaD50) were prolonged in sub-epicardial and M cells but shortened in sub-endocardial myocytes. These changes were significant at lower stimulus frequencies, but the relative effect diminished at higher frequencies (3 Hz). Peak systolic [Ca2+] was reduced in sub-epicardial and M cells but increased in sub-endocardial cells in the heart failure group compared to controls. At higher stimulus frequencies, end diastolic Ca2+ levels were lower in sub-epicardial cells but higher in sub-endocardial myocytes of the heart failure group compared with controls. In general, changes were greater in heart failure animals with more severe in vivo ventricular dysfunction (ejection fraction < or = 44%). CONCLUSIONS:Heart failure was associated with an increased cell size throughout the left ventricle, but the form of the changes in electrophysiology and Ca2+ transient were dependent on the myocyte sub-type. In particular sub-endocardial cells displayed markedly different changes compared to the other myocyte sub-types.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

McIntosh MA,Cobbe SM,Smith GL

doi

10.1016/s0008-6363(99)00360-0

subject

Has Abstract

pub_date

2000-01-14 00:00:00

pages

397-409

issue

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(99)00360-0

journal_volume

pub_type

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Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure.