Are B-type Ca 2+ Channels of Cardiac Myocytes Akin to the Passive Ion Channel in the Plasma Membrane Ca 2+ Pump?

Antoine, Sylvestre; Pinet, Caroline; Coulombe, Alain

doi:10.1007/s002320010035

Cited by 14 publications

(18 citation statements)

References 38 publications

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“…ref. 33), and also in native Ca 2ϩ -ATPases of surface (34) and sarcoplasmic reticular (35) membranes; the small flows in the latter case are consistent with an average channel P o on the order of 10…”

Section: Resultssupporting

confidence: 60%

Na ⁺ /K ⁺ -pump ligands modulate gating of palytoxin-induced ion channels

Artigas

Gadsby

2002

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

138

174

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The Na ؉ ͞K ؉ pump is a ubiquitous P-type ATPase that binds three cytoplasmic Na ؉ ions deep within its core where they are temporarily occluded before being released to the extracellular surface. The 3Na ؉ ͞2K ؉ -exchange transport cycle is completed when two extracellular K ؉ ions bind and become temporarily occluded within the protein and subsequently released to the cytoplasm. Coupling of Na ؉ -ion occlusion to phosphorylation of the pump by ATP and of K ؉ -ion occlusion to its dephosphorylation ensure the vectorial nature of net transport. The occluded-ion conformations, with binding sites inaccessible from either side, represent intermediate states in these alternating-access descriptions of transport. They afford protection against potentially catastrophic effects of inadvertently allowing simultaneous access from both membrane sides. The marine toxin, palytoxin, converts Na ؉ ͞K ؉ pumps into nonselective cation channels, possibly by disrupting the normal strict coupling between opening of one access pathway in the Na ؉ ͞K ؉ ATPase and closing of the other. We show here that gating of the channels in palytoxin-bound Na ؉ ͞K ؉ pumps in excised membrane patches is modulated by the pump's physiological ligands: cytoplasmic application of ATP promotes opening of the channels, and extracellular replacement of Na ؉ ions by K ؉ ions promotes closing of the channels. This suggests that, despite the presence of bound palytoxin, certain partial reactions of the normal Na ؉ ͞K ؉ -transport cycle persist and remain capable of effecting the conformational changes that control access to the pump's cation-binding sites. These findings affirm the alternatingaccess model of ion pumps and offer the possibility of examining ion occlusion͞deocclusion reactions in single pump molecules.

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Section: Resultssupporting

confidence: 60%

Na ⁺ /K ⁺ -pump ligands modulate gating of palytoxin-induced ion channels

Artigas

Gadsby

2002

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

138

174

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“…As an example, a decreased ATP-dependent Ca 2+ uptake has been shown to occur in PM vesicles isolated from hypertensive rat arterial smooth muscle (Kwan et al , 1980a(Kwan et al , 1980b, and in erythrocytes from animal and human models of hypertension (de la Sierra et al 1990;Vincenzi et al 1986;Postnov and Orlov 1983), and yet cultured hypertensive vascular smooth muscle cells show an increase in the levels of mRNA for PMCA (Monteith et al 1997). This matter is further confused by the observation that PMCA pump protein solubilized from erythrocytes and incorporated into liposomes has been shown to act under conditions like B-type Ca 2+ channels (Pinet et al 2002) that had been earlier reported in cardiac myocytes (Antoine et al 2001). …”

Section: Studies Using Transgenic Micementioning

confidence: 94%

Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors

Pande

Grover²

2005

Can. J. Physiol. Pharmacol.

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Plasma membrane Ca2+ pumps (PMCA pumps) are Ca2+-Mg2+ ATPases that expel Ca2+ from the cytosol to extracellular space and are pivotal to cell survival and function. PMCA pumps are encoded by the genes PMCA1, -2, -3, and -4. Alternative splicing results in a large number of isoforms that differ in their kinetics and activation by calmodulin and protein kinases A and C. Expression by 4 genes and a multifactorial regulation provide redundancy to allow for animal survival despite genetic defects. Heterozygous mice with ablation of any of the PMCA genes survive and only the homozygous mice with PMCA1 ablation are embryolethal. Some PMCA isoforms may also be involved in other cell functions. Biochemical and biophysical studies of PMCA pumps have been limited by their low levels of expression. Delineation of the exact physiological roles of PMCA pumps has been difficult since most cells also express sarco/endoplasmic reticulum Ca2+ pumps and a Na+-Ca2+-exchanger, both of which can lower cytosolic Ca2+. A major limitation in the field has been the lack of specific inhibitors of PMCA pumps. More recently, a class of inhibitors named caloxins have emerged, and these may aid in delineating the roles of PMCA pumps.

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“…The expanded-time scale trace designated "a" in Figure 5D shows the complex gating pattern of B-type channels, which was very similar to that previously observed with cardiac myocytes when B-type channel activity was in- duced by chlorpromazine. 31 Eosin (10 mol/L) completely blocked the channel activity ( Figure 5C), an effect characteristic of B-type Ca 2ϩ channels. 31 When channel recordings were made with mibefradil (20 mol/L) in the pipette, channel activities in freshly isolated and cultured CHF 147 VSMCs were markedly reduced (to 0.24 Ϯ 0.02 and 0.19 Ϯ 0.02, respectively; Figure 5E).…”

Section: Analysis Of B-type Channels In Vsmcs From Control and Chf 14mentioning

confidence: 99%

“…31 Eosin (10 mol/L) completely blocked the channel activity ( Figure 5C), an effect characteristic of B-type Ca 2ϩ channels. 31 When channel recordings were made with mibefradil (20 mol/L) in the pipette, channel activities in freshly isolated and cultured CHF 147 VSMCs were markedly reduced (to 0.24 Ϯ 0.02 and 0.19 Ϯ 0.02, respectively; Figure 5E). …”

Section: Analysis Of B-type Channels In Vsmcs From Control and Chf 14mentioning

confidence: 99%

Mutation of δ-Sarcoglycan Is Associated with Ca2+-Dependent Vascular Remodeling in the Syrian Hamster

Lipskaia

Pinet

Fromes

et al. 2007

The American Journal of Pathology

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We examined whether mutation of the ␦-sarcoglycan gene, which causes dilated cardiomyopathy, also alters the vascular smooth muscle cell (VSMC) phenotype and arterial function in the Syrian hamster CHF 147. Thoracic aorta media thickness showed marked variability in diseased hamsters with zones of atrophy and hypertrophied segments. CHF-147 VSMCs displayed a proliferating/"synthetic" phenotype characterized by the absence of the smooth muscle myosin heavy chain SM2, dystrophin, and Ca 2؉ -handling proteins, and the presence of cyclin D1. In freshly isolated VSMCs from CHF 147 hamsters, voltage-independent basal Ca 2؉ channels showed enhanced activity similar to that in proliferating wild-type (WT) cells. The transcription factor NFAT (nuclear factor of activated T cells) was spontaneously active in freshly isolated CHF 147 VSMCs, as in proliferating VSMCs from WT hamsters. Mibefradil inhibited B-type channels, NFAT activity, and VSMC proliferation. CHF 147 hamsters had abundant apoptotic cells distributed in patches along the aorta, and clusters of inactive mitochondria were observed in 25% of isolated CHF 147 cells, whereas no such clusters were seen in WT cells. In conclusion, mutation of the ␦-sarcoglycan gene increases plasma membrane permeability to Ca 2؉ , activates the Ca Disruption of the plasma membrane-associated sarcoglycan-sarcospan complex as a result of genetic defects causes muscular dystrophy and/or cardiomyopathy in humans (limb-girdle muscular dystrophy).1 There are six sarcoglycan family members: ␣-, ␤-, ␥-, ␦-, -, and -sarcoglycan.2 In hamster and mouse models, ␦-sarcoglycan gene deletion results in myopathy of cardiac and skeletal muscles, with focal areas of necrosis 3-5 and autophagic cardiomyocyte death. 6 Most of the studies on ␦-sarcoglycandeficient animals have been conducted on skeletal and cardiac muscles. The few studies on smooth muscle concerned the vasospasm of coronary arteries, but there are no data on the peripheral vessels. Sarcoglycans are transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix.7 At the cellular level, disruption of the dystrophinglycoprotein complex leads to increased permeability to divalent cations through channel-blocker-sensitive pathways and entry of calcium via nonspecific cation channels. 8 -11 The mechanisms of this enhanced Ca 2ϩ influx are not fully understood, but changes in the activity of several Ca 2ϩ channels have been described in dystrophin-deficient myocytes.12-15 Dystrophin, through PDZ domain-containing adaptor proteins known as syntrophins, can link the cytoskeleton to various membrane proteins carrying a PDZ domain, including ion channels. 16 This cytoskeleton-ion channel interaction contributes to receptor/channel localization and to the regulation of voltage-, ligand-, and storeoperated ion channels. Indeed, restoration of functional dystrophin-sarcoglycan complex formation by gene transfer of minidystrophin or ␦-sarcoglycan normalizes ion channel function in dystroph...

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Are B-type Ca 2+ Channels of Cardiac Myocytes Akin to the Passive Ion Channel in the Plasma Membrane Ca 2+ Pump?

Cited by 14 publications

References 38 publications

Na ⁺ /K ⁺ -pump ligands modulate gating of palytoxin-induced ion channels

Na ⁺ /K ⁺ -pump ligands modulate gating of palytoxin-induced ion channels

Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors

Mutation of δ-Sarcoglycan Is Associated with Ca2+-Dependent Vascular Remodeling in the Syrian Hamster

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Are B-type Ca 2+ Channels of Cardiac Myocytes Akin to the Passive Ion Channel in the Plasma Membrane Ca 2+ Pump?

Cited by 14 publications

References 38 publications

Na + /K + -pump ligands modulate gating of palytoxin-induced ion channels

Na + /K + -pump ligands modulate gating of palytoxin-induced ion channels

Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors

Mutation of δ-Sarcoglycan Is Associated with Ca2+-Dependent Vascular Remodeling in the Syrian Hamster

Contact Info

Product

Resources

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Na ⁺ /K ⁺ -pump ligands modulate gating of palytoxin-induced ion channels

Na ⁺ /K ⁺ -pump ligands modulate gating of palytoxin-induced ion channels