Activation of cardiac muscarinic receptor and ischemic preconditioning effects in in situ rat heart

Yamaguchi, Fuminari; Nasa, Yoshihisa; Yabe, Ken Ichi; Ohba, Shigeru; Hashizume, Yoko; Ohaku, Hisae; Furuhama, Ken Ichi; Takeo, Satoshi

doi:10.1007/bf02820870

Cited by 23 publications

(20 citation statements)

References 37 publications

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“…It may be related to stimulation of the muscarinic receptors. Several studies have demonstrated that stimulation of muscarinic receptors improves functional recovery of the heart after ischemia [23,24]. Therefore, it is conceivable that M3-mAChR could be a target for protecting the heart from ischemiainduced injury.…”

Section: Discussionmentioning

confidence: 99%

Ischemia Impairs the Association Between Connexin 43 and M3 Subtype of Acetylcholine Muscarinic Receptor (M3-mAChR) in Ventricular Myocytes

Yue

Zhang²,

Du³

et al. 2006

Cell Physiol Biochem

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We used Western blot analysis to examine the expression of connexin 43 and M2/M3 acetylcholine muscarinic receptors (mAChR) and their interaction in ventricular myocytes from control and the ischemic heart. We confirmed that the connexin 43 and M2/ M3-mAChR were expressed in ventricular myocytes. Moreover, we showed that M3-mAChR was expressed in non-glycosylated (72 kDa) and glycosylated forms (115 kDa). Immunostaining showed that connexin 43 is closely associated with M3-mAChR in parts of cell membranes of myocytes. Immunoprecipitation of lysate of cardiac myocytes with M2/M3-mAChR antibody pulled down a 44 kDa protein recognized by connexin 43 antibody. Ischemia increased the expression of M3-mAChR in myocytes. The ischemiainduced increase in the M3-mAChR expression was specific because ischemia did not affect the expression of M1, M2, M4 and M5- mAChR in the heart. On the other hand, ischemia decreased the expression of connexin 43 in myocardium. We also examined the effect of ischemia on the interaction between M2/M3-mAChR and connexin 43. Ischemia suppressed the association of M3-mAChR with connexin 43 but did not affect the association of connexin 43 with M2-mAChR. Administration of choline before ischemia not only partially restored the expression of connexin 43 but also attenuated the ischemia-induced suppression of the association between connexin 43 and M3-mAChR. We conclude that connexin 43 interacts with M2/M3-mAChR and that ischemia specifically impairs the association between M3-mAChR and connexin 43

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Section: Discussionmentioning

confidence: 99%

Ischemia Impairs the Association Between Connexin 43 and M3 Subtype of Acetylcholine Muscarinic Receptor (M3-mAChR) in Ventricular Myocytes

Yue

Zhang²,

Du³

et al. 2006

Cell Physiol Biochem

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“…In several studies, ACh was shown to be as potent as adenosine in protecting the myocardium against lethal ischemia/reperfusion injury (7, 59, 64, 80). Cardioprotection induced by ACh appears to be mediated via activation of muscarinic receptors and subsequent modulation of the activity of ATP-dependent potassium channels (7, 59, 80). …”

Section: Modulation Of Myocardial Ischemia/reperfusion Injury By Neurmentioning

confidence: 99%

Neural Mechanisms of Cardioprotection

Gourine

2014

Physiology

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“…These substances increase cGMP via direct stimulation of myocardial cells or via the endothelium. It was reported that the cGMP levels in preconditioned hearts are higher than in nonpreconditioned hearts (13)(14)(15). Since cGMP can induce protein phosphorylation via protein kinase G (PKG) activation, the involvement of PKG-dependent phosphorylation in ischemic preconditioning is expected.…”

mentioning

confidence: 99%

Modulation of ATP-sensitive Potassium Channels by cGMP-dependent Protein Kinase in Rabbit Ventricular Myocytes

Han

Kim

et al. 2001

Journal of Biological Chemistry

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This investigation used a patch clamp technique to test the hypothesis that protein kinase G (PKG) contributes to the phosphorylation and activation of ATP-sensitive K ؉ (K ATP ) channels in rabbit ventricular myocytes. Nitric oxide donors and PKG activators facilitated pinacidilinduced K ATP channel activities in a concentration-dependent manner, and a selective PKG inhibitor abrogated these effects. In contrast, neither a selective protein kinase A (PKA) activator nor inhibitor had any effect on K ATP channels at concentrations up to 100 and 10 M, respectively. Exogenous PKG, in the presence of both cGMP and ATP, increased channel activity, while the catalytic subunit of PKA had no effect. PKG activity was prevented by heat inactivation, replacing ATP with adenosine 5-O-(thiotriphosphate) (a nonhydrolyzable analog of ATP), removing Mg 2؉ from the internal solution, applying a PKG inhibitor, or by adding exogenous protein phosphatase 2A. The effects of cGMP analogs and PKG were observed under conditions in which PKA was repressed by a selective PKA inhibitor. The results suggest that K ATP channels are regulated by a PKG-signaling pathway that acts via PKG-dependent phosphorylation. This mechanism may, at least in part, contribute to a signaling pathway that induces ischemic preconditioning in rabbit ventricular myocytes.Protein phosphorylation is a putative effector mechanism in the infarct size-limiting effect of ischemic preconditioning (1), a phenomenon whereby a brief period of ischemia and reperfusion can protect the heart against subsequent prolonged ischemia and reperfusion injury (2). Indeed, it was shown that phosphorylation levels decrease during ischemia in nonpreconditioned hearts, whereas they increase during ischemia in preconditioned hearts (3). A number of cellular components, including cytoskeletal and stress proteins, have been proposed as potential phosphorylation targets in the ischemic preconditioned heart (4 -6).ATP-sensitive K ϩ channels (K ATP channels) 1 in sarcolemma and mitochondria are also modulated by phosphorylation (7, 8).The majority of the studies on the contribution of phosphorylation to K ATP channel activity to the cardioprotective effects of ischemic preconditioning have centered on the role of protein kinase C. Protein kinase C may act as a link between one or more receptor-mediated pathways and increased K ATP channel activity and thus lead to ischemic preconditioning (9). The release of endogenous substances, such as adenosine, bradykinin, nitric oxide (NO), and prostacyclin (10 -12), has been proposed as a potential mechanism of ischemic preconditioning. These substances increase cGMP via direct stimulation of myocardial cells or via the endothelium. It was reported that the cGMP levels in preconditioned hearts are higher than in nonpreconditioned hearts (13-15). Since cGMP can induce protein phosphorylation via protein kinase G (PKG) activation, the involvement of PKG-dependent phosphorylation in ischemic preconditioning is expected. To date, however, the role of PKG ...

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Activation of cardiac muscarinic receptor and ischemic preconditioning effects in in situ rat heart

Cited by 23 publications

References 37 publications

Ischemia Impairs the Association Between Connexin 43 and M3 Subtype of Acetylcholine Muscarinic Receptor (M3-mAChR) in Ventricular Myocytes

Ischemia Impairs the Association Between Connexin 43 and M3 Subtype of Acetylcholine Muscarinic Receptor (M3-mAChR) in Ventricular Myocytes

Neural Mechanisms of Cardioprotection

Modulation of ATP-sensitive Potassium Channels by cGMP-dependent Protein Kinase in Rabbit Ventricular Myocytes

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