Effects of ?1-adrenergic stimulation on normal and hypertrophied mouse hearts. Relation to caveolin-3 expression

Petrashevskaya, Natalia; Bódi, Ilona; Koch, Sheryl E.; Akhter, Shahab A.; Schwartz, Arnold

doi:10.1016/j.cardiores.2004.01.026

Cited by 15 publications

(10 citation statements)

References 34 publications

(39 reference statements)

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“…Several studies have demonstrated that α1-ARs were localized to the plasma membrane (19,33,34), whereas Wright et al (35) showed that α1-ARs were located around or within the nucleus, but not on the plasma membrane, in adult mouse cardiomyocytes. Thus, controversy exists regarding the localization of α1-ARs in cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors

Ogata

Naito

Nakanishi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as “caveolae.” Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR–induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

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Section: Discussionmentioning

confidence: 99%

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors

Ogata

Naito

Nakanishi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Contracting myocytes were equilibrated for 10 min in the presence of the ␤-AR antagonist timolol (10 M). Myocytes were then exposed to the ␣ 1-AR agonist phenylephrine (PE) at a dose (10 M) that mediates a near-maximal inotropic response in the mouse myocardium (13,19,21,26). In a subset of experiments, myocytes were exposed to the ␣ 1A-AR subtype-selective agonist A-61603 (100 nM).…”

Section: Methodsmentioning

confidence: 99%

Intraventricular and interventricular cellular heterogeneity of inotropic responses to α₁-adrenergic stimulation

Chu

Thai

Park

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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α1-Adrenergic receptors (α1-ARs) elicit a negative inotropic effect (NIE) in the mouse right ventricular (RV) myocardium but a positive inotropic effect (PIE) in the left ventricular (LV) myocardium. Effects on myofilament Ca(2+) sensitivity play a role, but effects on Ca(2+) handling could also contribute. We monitored the effects of α1-AR stimulation on contraction and Ca(2+) transients using single myocytes isolated from the RV or LV. Interestingly, for both the RV and LV, we found heterogeneous myocyte inotropic responses. α1-ARs mediated either a PIE or NIE, although RV myocytes had a greater proportion of cells manifesting a NIE (68%) compared with LV myocytes (36%). Stimulation of a single α1-AR subtype (α1A-ARs) with a subtype-selective agonist also elicited heterogeneous inotropic responses, suggesting that the heterogeneity arose from events downstream of the α1A-AR subtype. For RV and LV myocytes, an α1-AR-mediated PIE was associated with an increased Ca(2+) transient and a NIE was associated with a decreased Ca(2+) transient, suggesting a key role for Ca(2+) handling. For RV and LV myocytes, α1-AR-mediated decreases in the Ca(2+) transient were associated with increased Ca(2+) export from the cell and decreased Ca(2+) content of the sarcoplasmic reticulum. In contrast, for myocytes with α1-AR-induced increased Ca(2+) transients, sarcoplasmic reticulum Ca(2+) content was not increased, suggesting that other mechanisms contributed to the increased Ca(2+) transients. This study demonstrates the marked heterogeneity of LV and RV cellular inotropic responses to stimulation of α1-ARs and reveals a new aspect of biological heterogeneity among myocytes in the regulation of contraction.

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“…Stimulation of ␣-adrenergic receptors by phenylephine in Langendorff perfused mouse hearts in the presence of a ␤-blocker results in positive inotropic effect. 30,31 Moreover, it has been demonstrated in swine that acute hypercapnia was associated with release of both norepinephrine and epinephrine. 32 Plasma norepinephrine concentration increased 3.4-fold and epinephrine increased 1.8-fold compared with basal concentrations.…”

Section: Discussionmentioning

confidence: 99%

Expression of Slow Skeletal Troponin I in Adult Mouse Heart Helps to Maintain the Left Ventricular Systolic Function During Respiratory Hypercapnia

Urboniene

Dias

Peña

et al. 2005

Circulation Research

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Abstract-Compared with the adult, neonatal heart muscle is less sensitive to deactivation by acidic pH. We hypothesized that expression of slow skeletal troponin I (ssTnI), the embryonic isoform, in adult heart would help maintain left ventricular (LV) systolic function during respiratory hypercapnia. We assessed LV function by transthoracic 2D-targeted M-mode and pulsed Doppler echocardiography in transgenic (TG) mice in which cardiac TnI was replaced with ssTnI and in nontransgenic (NTG) littermates. Anesthetized mice were ventilated with either 100% oxygen or 35% CO 2 balanced with oxygen. Arterial blood pH with 35% CO 2 decreased to the same levels in both groups of animals.In the absence of propranolol, the LV fractional shortening was higher in TG compared with NTG mice throughout most of the experimental protocol. LV diastolic function was impaired in TG compared with NTG mice both at 100% oxygen and 35% CO 2 because E-to-A wave ratio of mitral flow was significantly lower, and E-wave deceleration time and LV isovolumic relaxation time were longer in TG compared with NTG mice. When compensatory mechanisms that occur through stimulation of ␤-adrenergic receptors during hypercapnia were blocked by continuous perfusion with propranolol, we found that NTG mice died within 3 to 4 minutes after switching to 35% CO 2 , whereas TG mice survived. Our experiments demonstrate the first evidence that specific replacement of cardiac TnI with ssTnI has a protective effect on the LV systolic function during hypercapnic acidosis in situ.

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Effects of ?1-adrenergic stimulation on normal and hypertrophied mouse hearts. Relation to caveolin-3 expression

Cited by 15 publications

References 34 publications

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors

Intraventricular and interventricular cellular heterogeneity of inotropic responses to α₁-adrenergic stimulation

Expression of Slow Skeletal Troponin I in Adult Mouse Heart Helps to Maintain the Left Ventricular Systolic Function During Respiratory Hypercapnia

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Effects of ?1-adrenergic stimulation on normal and hypertrophied mouse hearts. Relation to caveolin-3 expression

Cited by 15 publications

References 34 publications

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors

Intraventricular and interventricular cellular heterogeneity of inotropic responses to α1-adrenergic stimulation

Expression of Slow Skeletal Troponin I in Adult Mouse Heart Helps to Maintain the Left Ventricular Systolic Function During Respiratory Hypercapnia

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Intraventricular and interventricular cellular heterogeneity of inotropic responses to α₁-adrenergic stimulation