Return of calcium: Manipulating intracellular calcium to prevent cardiac pathologies

Wang, Yibin; Goldhaber, Joshua I.

doi:10.1073/pnas.0401518101

Cited by 21 publications

(14 citation statements)

References 36 publications

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“…Another source of triggered arrhythmias is early after depolarizations (EADs). In this case, arrhythmia is caused by prolongation of the action potential, an event that results in an excessive inward calcium current during each cardiac cycle (Wang and Goldhaber, 2004;Schotten et al, 2011). Thus, the mechanisms involved in intracellular calcium handling represent an interesting target for antiarrhythmic drugs.…”

Section: Discussionmentioning

confidence: 99%

“…spiralis is a plant traditionally used to treat hypertension and disturbances in cardiac rhythm. Curiously, these clinical dysfunctions involve changes in the intracellular calcium signaling cascades (Tostes and Wilde, 1997;Lompré, 1999;Wang and Goldhaber, 2004;Schotten et al, 2011). Calcium is ubiquitous in the regulation of cardiac excitation-contraction coupling.…”

Section: Discussionmentioning

confidence: 99%

“…It is important to mention that insufficient calcium influx leads to an inefficient cardiac contraction. On the other hand, excessive calcium entry should evoke cell death, contracture and generation of pathological membrane currents (Wang and Goldhaber, 2004). For these reasons, the cardiomyocytes have several control points to maintain calcium homeostasis.…”

Section: Discussionmentioning

confidence: 99%

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Aqueous fraction from Costus spiralis (Jacq.) Roscoe leaf reduces contractility by impairing the calcium inward current in the mammalian myocardium

Britto

Santos

Cruz

et al. 2011

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aqueous fraction from Costus spiralis (Jacq.) Roscoe leaf reduces contractility by impairing the calcium inward current in the mammalian myocardium

Britto

Santos

Cruz

et al. 2011

Journal of Ethnopharmacology

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“…Inward rectifier potassium channels conduct currents at voltages around the reversal potential, and can stabilize the resting membrane potential and repolarize the myocyte (Kaibara et al, 2002). An increase in the transcript for a calcium binding (calb3) protein was noted on day 2 and 5 in the 2 lower exposure levels, and this protein may help to control intracellular calcium levels, a critical function for maintaining cardiac function and cycling (Wang and Goldhaver, 2004;Wehrens et al, 2005) (Hagihara et al, 2005) Chacon et al, 2001. At the high CEM exposure level the heart was unable to launch this response.…”

Section: Histopathologymentioning

confidence: 99%

Critical Pathways in Heart Function: Bis(2-chloroethoxy)methane-Induced Heart Gene Transcript Change in F344 Rats

et al. 2006

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Gene transcript changes after exposure to the heart toxin, bis(2-chloroethoxy)methane (CEM), were analyzed to elucidate mechanisms in cardiotoxicity and recovery. CEM was administered to 5-week-old male F344/N rats at 0, 200, 400, or 600 mg/kg by dermal exposure, 5 days per week, for a total of 12 doses by study day 16. Heart toxicity occurred after 2 days of dosing in all 3 regions of the heart (atrium, ventricle, interventricular septum) and was characterized by myofiber vacuolation, necrosis, mononuclear-cell infiltration, and atrial thrombosis. Ultrastructural analysis revealed that the primary site of damage was the mitochondrion. By day 5, even though dosing was continued, the toxic lesions in the heart began to resolve, and by study day 16, the heart appeared histologically normal. RNA was extracted from whole hearts after 2 or 5 days of CEM dosing. After a screen for transcript change by microarray analysis, dose-response trends for selected transcripts were analyzed by qRT-PCR. The selected transcripts code for proteins involved in energy production, control of calcium levels, and maintenance of heart function. The down-regulation of ATP subunit transcripts (Atp5j, ATP5k), which reside in the mitochondrial membranes, indicated a decrease in energy supply at day 2 and day 5. This was accompanied by down-regulation of transcripts involved in high-energy consumption processes such as membrane transport and ion channel transcripts (e.g., abc1a, kcnj12). The up-regulation of transcripts encoding for temperature regulation and calcium binding proteins (ucp1 and calb3) only at the 2 low exposure levels, suggest that these adaptive processes cannot occur in association with severe cardiotoxicity as seen in hearts at the high exposure level. Transcript expression changes occurred within 2 days of CEM exposure, and were dose-and time-dependent. The heart transcript changes suggest that CEM cardiotoxicity activates protective processes associated energy conservation and maintenance of heart function.

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“…This adverse signaling chain leads from the b-adrenergic receptor via adenyl cyclase to formation of cyclic AMP, activation of protein kinase A (PKA), increased opening of the L-type calcium current, 3 and ultimately an increase in cytosolic calcium, the latter being potentially harmful. [4][5][6] cAMP itself can mimic the structural damage caused by excessive b-adrenergic stimulation. 7 Conversely, attenuation of cAMP accumulation during prolonged ischemia may contribute to improved post-ischemic recovery.…”

mentioning

confidence: 98%

H-89, a Non-Specific Inhibitor of Protein Kinase A, Promotes Post-Ischemic Cardiac Contractile Recovery and Reduces Infarct Size

Makaula¹,

Lochner²,

Genade³

et al. 2005

Journal of Cardiovascular Pharmacology

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Myocardial ischemia is associated with increased production of cyclic adenosine monophosphate (cAMP), with potentially deleterious effects. We hypothesized that the ischemia-induced activation of cAMP-dependent protein kinase A (PKA), could beneficially be inhibited by a PKA-inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinoline-sulfonamide (H-89). H-89 when given to isolated perfused rat hearts before 30 minutes of global ischemia-reperfusion improved postischemic function and decreased infarct size. In another series, H-89 administered prior to preconditioning by 10 minutes of transient global ischemia decreased PKA activity (measured at the end of the preconditioning protocol) and augmented postischemic mechanical recovery. H-89 given for 5 minutes before the 10 minutes of transient ischemia further decreased infarct size from 13.4 +/- 1.0% (preconditioning alone) to 7.0 +/- 0.93 (P < 0.01). In a third series, forskolin (0.3 muM, 5 minutes, 10 minutes washout prior to ischemia) increased PKA activity and reduced infarct size. Prior H-89 decreased PKA activity after 5 minutes of forskolin and further reduced infarct size versus forskolin alone. In conclusion, three procedures increased postischemic recovery and reduced infarct size: H-89; preconditioning by transient ischemia; or forskolin as a preconditioning-mimetic. PKA-inhibition by H-89 further decreased infarct size beyond preconditioning or forskolin. Despite the reservation that H-89 could be non-selective in its actions, we propose H-89 as a candidate cardioprotective agent.

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Return of calcium: Manipulating intracellular calcium to prevent cardiac pathologies

Cited by 21 publications

References 36 publications

Aqueous fraction from Costus spiralis (Jacq.) Roscoe leaf reduces contractility by impairing the calcium inward current in the mammalian myocardium

Aqueous fraction from Costus spiralis (Jacq.) Roscoe leaf reduces contractility by impairing the calcium inward current in the mammalian myocardium

Critical Pathways in Heart Function: Bis(2-chloroethoxy)methane-Induced Heart Gene Transcript Change in F344 Rats

H-89, a Non-Specific Inhibitor of Protein Kinase A, Promotes Post-Ischemic Cardiac Contractile Recovery and Reduces Infarct Size

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