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Different effects of alpha- and beta-adrenergic stimulation on cytosolic pH and myofilament responsiveness to Ca2+ in cardiac myocytes.

Abstract：

:alpha-Adrenergic stimulation (alpha-AS) and beta-adrenergic stimulation (beta-AS) of the myocardium are associated respectively with an increase and a decrease in myofilament responsiveness to Ca2+. We hypothesized that changes in cytosolic pH (pH(i)) may modulate these opposite actions of alpha-AS and beta-AS. The effects of alpha-AS (50 microM phenylephrine and 1 microM nadolol) and beta-AS (0.05 microM isoproterenol) on contraction and either cytosolic Ca2+ (Cai) or pH(i) were assessed in adult rat ventricular myocytes bathed in bicarbonate buffer (pH 7.36 +/- 0.05). In cells loaded with the ester derivative (AM form) of indo-1, the 410/490-nm ratio of emitted fluorescence indexed Cai. Myofilament responsiveness to Ca2+ was assessed by the relaxation phase of the length-indo-1 fluorescence relation during a twitch. alpha-AS and beta-AS shifted this relation in opposite directions, indicating that alpha-AS increased and beta-AS decreased myofilament responsiveness to Ca2+. In addition, the positive inotropic action of alpha-AS was associated with an increased Cai transient amplitude in 50% of the myocytes (n = 12), whereas beta-AS always increased Cai (n = 5). In cells loaded with the fluorescent pH(i) probe SNARF-1 AM, the emitted 590/640-nm fluorescence is a measure of pH(i). The effect of alpha-AS on the extent of cell shortening during the twitch (ES) was expressed as the percentage of resting cell length. Both ES and pH(i) were assessed in myocytes bathed in 1.5 mM [Ca2+] and stimulated at 0.5 Hz (control ES, 7.4 +/- 1.5%; control pH(i), 7.11 +/- 0.05; n = 10). alpha-AS enhanced both ES (delta ES, 1.8 +/- 0.6%; p less than 0.05) and pH(i) (delta pH(i), 0.06 +/- 0.01; p less than 0.005), and there was a significant correlation between delta ES and delta pH(i) (r = 0.76, p less than 0.05). A similar effect of alpha-AS on pH(i) was observed in the absence of electrical stimulation (n = 8). The alpha-AS-induced enhancement of ES and pH(i) was abolished by 10 microM ethylisopropylamiloride, a Na(+)-H+ exchange inhibitor (n = 7). In additional experiments, myocytes were preincubated either with 0.2 microM 4 beta-phorbol 12-myristate 13-acetate (n = 8) or with 5 nM staurosporine (n = 8), which have been shown to downregulate and inhibit Ca(2+)-activated phospholipid-dependent protein kinase C, respectively. In either group, alpha-AS had no effect on pH(i) and decreased ES to approximately 60% of control.(ABSTRACT TRUNCATED AT 400 WORDS)

journal_name

Circ Res

journal_title

Circulation research

authors

Gambassi G,Spurgeon HA,Lakatta EG,Blank PS,Capogrossi MC

doi

10.1161/01.res.71.4.870

subject

Has Abstract

pub_date

1992-10-01 00:00:00

pages

870-82

issue

eissn

0009-7330

issn

1524-4571

journal_volume

pub_type

杂志文章

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Different effects of alpha- and beta-adrenergic stimulation on cytosolic pH and myofilament responsiveness to Ca2+ in cardiac myocytes.