Ca2+ Channels Mediate Bidirectional Signaling between Sarcolemma and Sarcoplasmic Reticulum in Muscle Cells

Ávila, Guillermo; Rosa, Juan A de la; Monsalvo-Villegas, Adrián; Montiel-Jaen, María Guadalupe

doi:10.3390/cells9010055

Cited by 23 publications

(18 citation statements)

References 157 publications

(160 reference statements)

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“…High voltage-activated, dihydropyridine-sensitive L-type calcium channels are involved in excitation-contraction coupling in skeletal, smooth, and cardiac myocytes as well as the release of neurotransmitters and hormones from neurons and endocrine cells [ 93 , 94 ]. It has been demonstrated via biochemical assays that AEA is able to displace specific binding of L-type calcium channel antagonists to rabbit skeletal muscle membranes in a concentration-dependent manner, with the IC 50 around 4–30 μM [ 88 ], supporting a direct interaction between AEA and L-type calcium channels.…”

Section: Discussionmentioning

confidence: 99%

Potassium channels as molecular targets of endocannabinoids

Lin

2021

Channels

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Endocannabinoids are a group of endogenous mediators derived from membrane lipids, which are implicated in a wide variety of physiological functions such as blood pressure regulation, immunity, pain, memory, reward, perception, reproduction, and sleep. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) represent two major endocannabinoids in the human body and they exert many of their cellular and organ system effects by activating the G i/o protein-coupled, cannabinoid type 1 (CB1) and type 2 (CB2) receptors. However, not all effects of cannabinoids are ascribable to their interaction with CB1 and CB2 receptors; indeed, macromolecules like other types of receptors, ion channels, transcription factors, enzymes, transporters, and cellular structure have been suggested to mediate the functional effects of cannabinoids. Among the proposed molecular targets of endocannabinoids, potassium channels constitute an intriguing group, because these channels not only are crucial in shaping action potentials and controlling the membrane potential and cell excitability, thereby regulating a wide array of physiological processes, but also serve as potential therapeutic targets for the treatment of cancer and metabolic, neurological and cardiovascular disorders. This review sought to survey evidence pertaining to the CB1 and CB2 receptorindependent actions of endocannabinoids on ion channels, with an emphasis on AEA and potassium channels. To better understand the functional roles as well as potential medicinal uses of cannabinoids in human health and disease, further mechanistic studies to delineate interactions between various types of cannabinoids and ion channels, including members in the potassium channel superfamily, are warranted.

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Section: Discussionmentioning

confidence: 99%

Potassium channels as molecular targets of endocannabinoids

Lin

2021

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“…The function of mitochondria and CRUs, besides being important for providing independently ATP and Ca 2+ , is also controlled by their cross-communication: indeed, the importance of a close structural association between intracellular Ca 2+ stores (ER and SR) and mitochondria has been described and discussed extensively in the last couple of decades in both non-excitable and excitable cells [11][12][13][14][15][16][17]. The SR-mitochondria cross-talk in striated tissues has been proposed to be bidirectional [18]: Ca 2+ released by the CRUs enters mitochondria via the mitochondrial Ca 2+ uniporter (MCU) to stimulate the respiratory chain, while the reactive oxygen species (ROS) produced by mitochondria can regulate SR Ca 2+ release [18].…”

Section: Introductionmentioning

confidence: 99%

Ageing Causes Ultrastructural Modification to Calcium Release Units and Mitochondria in Cardiomyocytes

d’Onofrio

Fonso

Protasi

et al. 2021

IJMS

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Ageing is associated with an increase in the incidence of heart failure, even if the existence of a real age-related cardiomyopathy remains controversial. Effective contraction and relaxation of cardiomyocytes depend on efficient production of ATP (handled by mitochondria) and on proper Ca2+ supply to myofibrils during excitation–contraction (EC) coupling (handled by Ca2+ release units, CRUs). Here, we analyzed mitochondria and CRUs in hearts of adult (4 months old) and aged (≥24 months old) mice. Analysis by confocal and electron microscopy (CM and EM, respectively) revealed an age-related loss of proper organization and disposition of both mitochondria and EC coupling units: (a) mitochondria are improperly disposed and often damaged (percentage of severely damaged mitochondria: adults 3.5 ± 1.1%; aged 16.5 ± 3.5%); (b) CRUs that are often misoriented (longitudinal) and/or misplaced from the correct position at the Z line. Immunolabeling with antibodies that mark either the SR or T-tubules indicates that in aged cardiomyocytes the sarcotubular system displays an extensive disarray. This disarray could be in part caused by the decreased expression of Cav-3 and JP-2 detected by western blot (WB), two proteins involved in formation of T-tubules and in docking SR to T-tubules in dyads. By WB analysis, we also detected increased levels of 3-NT in whole hearts homogenates of aged mice, a product of nitration of protein tyrosine residues, recognized as marker of oxidative stress. Finally, a detailed EM analysis of CRUs (formed by association of SR with T-tubules) points to ultrastructural modifications, i.e., a decrease in their frequency (adult: 5.1 ± 0.5; aged: 3.9 ± 0.4 n./50 μm2) and size (adult: 362 ± 40 nm; aged: 254 ± 60 nm). The changes in morphology and disposition of mitochondria and CRUs highlighted by our results may underlie an inefficient supply of Ca2+ ions and ATP to the contractile elements, and possibly contribute to cardiac dysfunction in ageing.

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“…Thus, SR Ca 2+ cycling is not only important for muscle contraction and relaxation cycle but also helps to maintain cytosolic Ca 2+ levels. For extensive reviews on Ca 2+ handling in normal skeletal muscle and heart, refer to the recent reviews (Endo, 2009;Lee, 2010;Eisner et al, 2017;Avila et al, 2019).…”

Section: Calcium Handling In Normal Musclementioning

confidence: 99%

Abnormal Calcium Handling in Duchenne Muscular Dystrophy: Mechanisms and Potential Therapies

et al. 2021

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Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by the loss of dystrophin. DMD is associated with muscle degeneration, necrosis, inflammation, fatty replacement, and fibrosis, resulting in muscle weakness, respiratory and cardiac failure, and premature death. There is no curative treatment. Investigations on disease-causing mechanisms offer an opportunity to identify new therapeutic targets to treat DMD. An abnormal elevation of the intracellular calcium (Cai2+) concentration in the dystrophin-deficient muscle is a major secondary event, which contributes to disease progression in DMD. Emerging studies have suggested that targeting Ca2+-handling proteins and/or mechanisms could be a promising therapeutic strategy for DMD. Here, we provide an updated overview of the mechanistic roles the sarcolemma, sarcoplasmic/endoplasmic reticulum, and mitochondria play in the abnormal and sustained elevation of Cai2+ levels and their involvement in DMD pathogenesis. We also discuss current approaches aimed at restoring Ca2+ homeostasis as potential therapies for DMD.

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Ca2+ Channels Mediate Bidirectional Signaling between Sarcolemma and Sarcoplasmic Reticulum in Muscle Cells

Cited by 23 publications

References 157 publications

Potassium channels as molecular targets of endocannabinoids

Potassium channels as molecular targets of endocannabinoids

Ageing Causes Ultrastructural Modification to Calcium Release Units and Mitochondria in Cardiomyocytes

Abnormal Calcium Handling in Duchenne Muscular Dystrophy: Mechanisms and Potential Therapies

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