All Outputs (17)

Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens (2024)
Journal Article
Asunción-Alvarez, D., Palacios, J., Ybañez-Julca, R. O., Rodriguez-Silva, C. N., Nwokocha, C., Cifuentes, F., & Greensmith, D. J. (2024). Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens. American journal of physiology. Heart and circulatory physiology, 326(4), H950-H970. https://doi.org/10.1152/ajpheart.00600.2023

Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca2+ concentrations are often influenced by sex differences. Furthermore, a... Read More about Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens.

Boswellia carterii oleoresin extracts induce caspase-mediated apoptosis and G 1 cell cycle arrest in human leukaemia subtypes (2023)
Journal Article
Jones, M. A., Borun, A., & Greensmith, D. J. (2023). Boswellia carterii oleoresin extracts induce caspase-mediated apoptosis and G 1 cell cycle arrest in human leukaemia subtypes. Frontiers in Pharmacology, 14, 1282239. https://doi.org/10.3389/fphar.2023.1282239

Background: Leukemias are a common cancer in adults and children. While existing treatments are effective, they are associated with severe side-effects compounded by the emergence of drug resistance. This necessitates the need to develop new drugs an... Read More about Boswellia carterii oleoresin extracts induce caspase-mediated apoptosis and G 1 cell cycle arrest in human leukaemia subtypes.

A hydroalcoholic extract of Senecio nutans SCh. Bip (Asteraceae); its effects on cardiac function and chemical characterization (2022)
Journal Article
Palacios, J., Paredes, A., Cifuentes, F., Catalan, M., Garcia-Villalon, A., Borquez, J., …Greensmith, D. (2023). A hydroalcoholic extract of Senecio nutans SCh. Bip (Asteraceae); its effects on cardiac function and chemical characterization. Journal of Ethnopharmacology, 300, https://doi.org/10.1016/j.jep.2022.115747

Ethnopharmacology relevance The plant Senecio nutans SCh. Bip. is used by Andean communities to treat altitude sickness. Recent evidence suggests it may produce vasodilation and negative cardiac inotropy, though the cellular mechanisms have not been... Read More about A hydroalcoholic extract of Senecio nutans SCh. Bip (Asteraceae); its effects on cardiac function and chemical characterization.

Systolic [Ca2+ ]i regulates diastolic levels in rat ventricular myocytes (2017)
Journal Article
Sankaranarayanan, R., Kistamas, K., Greensmith, D., Venetucci, L., & Eisner, D. (2017). Systolic [Ca2+ ]i regulates diastolic levels in rat ventricular myocytes. Journal of Physiology, 595(16), 5545-5555. https://doi.org/10.1113/JP274366

[Ca2+]i must be low enough in diastole so that the ventricle is relaxed and can refill with blood. Interference with this will impair relaxation. The factors responsible for regulation of diastolic [Ca2+]i, in particular the relative roles of the sar... Read More about Systolic [Ca2+ ]i regulates diastolic levels in rat ventricular myocytes.

Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank–Starling response (2016)
Journal Article
Scotcher, J., Prysyazhna, O., Boguslavskyi, A., Kistamas, K., Hadgraft, N., Martin, E., …Eaton, P. (2016). Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank–Starling response. Nature communications, 7, 13187. https://doi.org/10.1038/ncomms13187

The Frank–Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and o... Read More about Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank–Starling response.

Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak (2015)
Journal Article
Sankaranarayanan, R., Li, Y., Greensmith, D., Eisner, D., & Venetucci, L. (2016). Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak. Journal of Physiology, 594(3), 611-623. https://doi.org/10.1113/JP271473

In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have c... Read More about Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak.

The effect of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBQ) on intracellular Ca(2+) handling in rat ventricular myocytes (2015)
Journal Article
Miller, L., Greensmith, D., Sankaranarayanan, R., O'Neill, S., & Eisner, D. (2015). The effect of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBQ) on intracellular Ca(2+) handling in rat ventricular myocytes. Cell Calcium, 58(2), 208-14. https://doi.org/10.1016/j.ceca.2015.05.002

2,5-Di-(tert-butyl)-1,4-benzohydroquinone (TBQ) is a reversible inhibitor of SERCA, potentially making it a useful tool to study the effects of SERCA inhibition in cardiac cells. However, it is unknown if TBQ also has effects on other components of v... Read More about The effect of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBQ) on intracellular Ca(2+) handling in rat ventricular myocytes.

Perturbed atrial calcium handling in an ovine model of heart failure : potential roles for reductions in the L-type calcium current (2014)
Journal Article
Clarke, J., Caldwell, J., Horn, M., Bode, E., Richards, M., Hall, M., …Trafford, A. (2015). Perturbed atrial calcium handling in an ovine model of heart failure : potential roles for reductions in the L-type calcium current. Journal of Molecular and Cellular Cardiology, 79, 169-179. https://doi.org/10.1016/j.yjmcc.2014.11.017

Heart failure (HF) is commonly associated with reduced cardiac output and an increased risk of atrial arrhythmias particularly during β-adrenergic stimulation. The aim of the present study was to determine how HF alters systolic Ca(2+) and the respon... Read More about Perturbed atrial calcium handling in an ovine model of heart failure : potential roles for reductions in the L-type calcium current.

Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors (2014)
Journal Article
Dubuis, E., Thompson, V., Leite, M., Blaes, F., Maihöfner, C., Greensmith, D., …Goebel, A. (2014). Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors. PAIN, 155(11), 2408-2417. https://doi.org/10.1016/j.pain.2014.09.022

Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a... Read More about Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors.

The effects of 2',5'-di(tert-butyl)-1,4-benzohydroquinone (TBQ) on calcium handling in rat ventricular myocytes (2014)
Journal Article
Greensmith, D., Miller, L., & Eisner, D. (2014). The effects of 2',5'-di(tert-butyl)-1,4-benzohydroquinone (TBQ) on calcium handling in rat ventricular myocytes. Proceedings of the Physiological Society (Online), 31, PCA042

2',5'-di(tert-butyl)-1,4-benzohydroquinone (TBQ) is a reversible inhibitor of SERCA, potentially making it a useful tool to study the effects of SERCA inhibition. It has been used in a variety of cell types including ventricular myocytes (1). However... Read More about The effects of 2',5'-di(tert-butyl)-1,4-benzohydroquinone (TBQ) on calcium handling in rat ventricular myocytes.

Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions (2014)
Journal Article
Greensmith, D., Galli, G., Trafford, A., & Eisner, D. (2014). Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions. Cardiovascular Research, 103(4), 554-563. https://doi.org/10.1093/cvr/cvu158

AIMS: Most of the calcium that activates contraction is released from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR). It is controversial whether activators of the RyR produce a maintained increase in the amplitude of the systol... Read More about Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions.

Ca analysis : an Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis (2013)
Journal Article
Greensmith, D. (2014). Ca analysis : an Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis. Computer Methods and Programs in Biomedicine, 113(1), 241-250. https://doi.org/10.1016/j.cmpb.2013.09.004

Here I present an Excel based program for the analysis of intracellular Ca transients recorded using fluorescent indicators. The program can perform all the necessary steps which convert recorded raw voltage changes into meaningful physiological info... Read More about Ca analysis : an Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis.

The effects of tumor necrosis factor-alpha on systolic and diastolic function in rat ventricular myocytes (2013)
Journal Article
Greensmith, D., & Nirmalan, M. (2013). The effects of tumor necrosis factor-alpha on systolic and diastolic function in rat ventricular myocytes. Physiological Reports, 1(4), e00093. https://doi.org/10.1002/phy2.93

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is associated with myocardial dysfunction observed in sepsis and septic shock. There are two fundamental components to this dysfunction. (1) systolic dysfunction; and (2) diastolic dysf... Read More about The effects of tumor necrosis factor-alpha on systolic and diastolic function in rat ventricular myocytes.

Diastolic spontaneous calcium release from the sarcoplasmic reticulum increases beat-to-beat variability of repolarization in canine ventricular myocytes after β-adrenergic stimulation (2013)
Journal Article
Johnson, D., Heijman, J., Bode, E., Greensmith, D., van der Linde, H., Abi-Gerges, N., …Volders, P. (2013). Diastolic spontaneous calcium release from the sarcoplasmic reticulum increases beat-to-beat variability of repolarization in canine ventricular myocytes after β-adrenergic stimulation. Circulation Research, 112(2), 246-56. https://doi.org/10.1161/CIRCRESAHA.112.275735

RATIONALE Spontaneous Ca(2+) release (SCR) from the sarcoplasmic reticulum can cause delayed afterdepolarizations and triggered activity, contributing to arrhythmogenesis during β-adrenergic stimulation. Excessive beat-to-beat variability of repol... Read More about Diastolic spontaneous calcium release from the sarcoplasmic reticulum increases beat-to-beat variability of repolarization in canine ventricular myocytes after β-adrenergic stimulation.

Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: collagen accumulation in the young and loss in the aged (2012)
Journal Article
Horn, M., Graham, H., Richards, M., Clarke, J., Greensmith, D., Briston, S., …Trafford, A. (2012). Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: collagen accumulation in the young and loss in the aged. Journal of Molecular and Cellular Cardiology, 53(1), 82-90. https://doi.org/10.1016/j.yjmcc.2012.03.011

The incidence of heart failure (HF) increases with age. This study sought to determine whether aging exacerbates structural and functional remodeling of the myocardium in HF. HF was induced in young (~18 months) and aged sheep (>8 years) by right ven... Read More about Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: collagen accumulation in the young and loss in the aged.

Impaired β-adrenergic responsiveness accentuates dysfunctional excitation-contraction coupling in an ovine model of tachypacing-induced heart failure (2011)
Journal Article
Briston, S., Caldwell, J., Horn, M., Clarke, J., Richards, M., Greensmith, D., …Trafford, A. (2011). Impaired β-adrenergic responsiveness accentuates dysfunctional excitation-contraction coupling in an ovine model of tachypacing-induced heart failure. Journal of Physiology, 589(Pt 6), 1367-82. https://doi.org/10.1113/jphysiol.2010.203984

Reduced inotropic responsiveness is characteristic of heart failure (HF). This study determined the cellular Ca2+ homeostatic and molecular mechanisms causing the blunted β-adrenergic (β-AR) response in HF.We induced HF by tachypacing in sheep; intra... Read More about Impaired β-adrenergic responsiveness accentuates dysfunctional excitation-contraction coupling in an ovine model of tachypacing-induced heart failure.

The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte (2010)
Journal Article
Greensmith, D., Eisner, D., & Nirmalan, M. (2010). The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte. Cell Calcium, 48(6), 341-51. https://doi.org/10.1016/j.ceca.2010.10.007

Elevations in reactive oxygen species are implicated in many disease states and cause systolic and diastolic myocardial dysfunction. To understand the underlying cellular dysfunction, we characterised the effects of H₂O₂ on [Ca(2+)](i) handling and c... Read More about The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte.