Imperial College London

ProfessorSianHarding

Faculty of MedicineNational Heart & Lung Institute

Emeritus Professor of Cardiac Pharmacology
 
 
 
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Contact

 

+44 (0)20 7594 3009sian.harding Website

 
 
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Location

 

435ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

464 results found

Rau T, Nose M, Remmers U, Weil J, Weissmüller A, Davia K, Harding S, Peppel K, Koch WJ, Eschenhagen Tet al., 2003, Overexpression of wild-type Gαi-2 suppresses β-adrenergic signaling in cardiac myocytes, FASEB JOURNAL, Vol: 17, Pages: 523-+, ISSN: 0892-6638

Journal article

El-Armouche A, Rau T, Zolk O, Ditz D, Pamminger T, Zimmermann WH, Jäckel E, Harding SE, Boknik P, Neumann J, Eschenhagen Tet al., 2003, Evidence for protein phosphatase inhibitor-1 playing an amplifier role in β-adrenergic signaling in cardiac myocytes, FASEB JOURNAL, Vol: 17, Pages: 437-+, ISSN: 0892-6638

Journal article

Chaudhri B, Del Monte F, Hajjar RJ, Harding SEet al., 2002, Interaction between increased SERCA2a activity and β-adrenoceptor stimulation in adult rabbit myocytes, American Journal of Physiology - Heart and Circulatory Physiology, Vol: 283, ISSN: 0363-6135

Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a overexpression and phospholamban depletion have been shown to have beneficial effects on contractility in heart failure. However, the high sympathetic tone during development of failure may interact with increases in SERCA2a activity in potentially deleterious ways. We used adenoviral vectors to overexpress SERCA2a or partially downregulate phospholamban in adult rabbit ventricular myocytes in culture and studied the responses of these cells to β-adrenoceptor stimulation. SERCA2a overexpression and phospholamban depletion had quantitatively similar effects on basal contraction amplitude and in accelerating relaxation. Increasing SERCA2a activity by either strategy had little effect on the increase in contraction amplitude or incidence of arrhythmias with increasing isoproterenol. Maximum acceleration of relaxation by β-adrenoceptor stimulation was similar to that produced by SERCA2a overexpression. Isoproterenol treatment of SERCA2a-overexpressing or phospholamban-deficient myocytes produced a further modest decrease in relaxation time, with similar final values in both groups. We find no evidence for Ca2+ overload induced by SERCA2a overexpression alone or in combination with catecholamines.

Journal article

Lewis CJ, Gong H, Koch WJ, Brown MJ, Harding SEet al., 2002, Adenovirally-overexpressed beta 2-adrenoceptors enhance the contractile response to CGP 12177A in adult rat cardiomyocytes, Meeting of the British-Pharmacological-Society, Publisher: NATURE PUBLISHING GROUP, ISSN: 0007-1188

Conference paper

Chaudhri B, Del Monte F, Hajjar RJ, Harding SEet al., 2002, Interaction between increased SERCA2a activity and β-adrenoceptor stimulation in adult rabbit myocytes, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 283, Pages: H2450-H2457, ISSN: 0363-6135

Journal article

Harding SE, Del Monte F, 2002, Dissociation of hypertrophic growth from changes in myocyte contractile function, JOURNAL OF CARDIAC FAILURE, Vol: 8, Pages: S415-S420, ISSN: 1071-9164

Journal article

Gorelik J, Gu YC, Spohr HA, Shevchuk AI, Lab MJ, Harding SE, Edwards CRW, Whitaker M, Moss GWJ, Benton DCH, Sánchez D, Darszon A, Vodyanoy I, Klenerman D, Korchev YEet al., 2002, Ion channels in small cells and subcellular structures can be studied with a smart patch-clamp system, BIOPHYSICAL JOURNAL, Vol: 83, Pages: 3296-3303, ISSN: 0006-3495

Journal article

Pathan N, Sandiford C, Harding SE, Levin Met al., 2002, Characterization of a myocardial depressant factor in meningococcal septicemia, CRITICAL CARE MEDICINE, Vol: 30, Pages: 2191-2198, ISSN: 0090-3493

Journal article

Gorelik J, Harding SE, Shevchuk AI, Koralage D, Lab M, de Swiet M, Korchev Y, Williamson Cet al., 2002, Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics, CLINICAL SCIENCE, Vol: 103, Pages: 191-200, ISSN: 0143-5221

Journal article

Terracciano CMN, Hajjar RJ, Harding SE, 2002, Overexpression of SERCA2a accelerates repolarisation in rabbit ventricular myocytes, CELL CALCIUM, Vol: 31, Pages: 299-305, ISSN: 0143-4160

Journal article

Gong HB, Sun H, Koch WJ, Rau T, Eschenhagen T, Ravens U, Heubach JF, Adamson DL, Harding SEet al., 2002, Specific β<sub>2</sub>AR blocker ICI 118,551 actively decreases contraction through a G<sub>i</sub>-coupled form of the β<sub>2</sub>AR in myocytes from failing human heart, CIRCULATION, Vol: 105, Pages: 2497-2503, ISSN: 0009-7322

Journal article

Ranu HK, Terracciano CMN, Davia K, Bernobich E, Chaudhri B, Robinson SE, Kang ZB, Hajjar RJ, MacLeod KT, Harding SEet al., 2002, Effects of Na<SUP>+</SUP>/Ca<SUP>2+</SUP>-exchanger overexpression on excitation-contraction coupling in adult rabbit ventricular myocytes, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 34, Pages: 389-400, ISSN: 0022-2828

Journal article

Gu YC, Gorelik J, Spohr HA, Shevchuk A, Lab MJ, Harding SE, Vodyanoy I, Klenerman D, Korchev YEet al., 2002, High-resolution scanning patch-clamp: new insights into cell function, FASEB JOURNAL, Vol: 16, Pages: 748-+, ISSN: 0892-6638

Journal article

del Monte F, Harding SE, Dec GW, Gwathmey JK, Hajjar RJet al., 2002, Targeting phospholamban by gene transfer in human heart failure, CIRCULATION, Vol: 105, Pages: 904-907, ISSN: 0009-7322

Journal article

Song GJ, Harding SE, Duchen MR, Tunwell R, O'Gara P, Hawkins TE, Moss SEet al., 2002, Altered mechanical properties and intracellular calcium signaling in cardiomyocytes from annexin 6 null-mutant mice, FASEB JOURNAL, Vol: 16, Pages: 622-+, ISSN: 0892-6638

Journal article

Song G, Harding SE, Duchen MR, Tunwell R, O'Gara P, Hawkins TE, Moss SEet al., 2002, Altered mechanical properties and intracellular calcium signaling in cardiomyocytes from annexin 6 null-mutant mice., The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol: 16, Pages: 622-624

Annexin 6 is one of a widely expressed family of calcium-binding proteins found in most mammalian tissues, including the heart. Several studies have implicated annexin 6 in the regulation of intracellular Ca2+ signaling, and it has been shown in vitro to act as a modulator of the sarcoplasmic reticulum Ca2+-release channel, cardiac L-type calcium channel, and Na+/Ca2+ exchanger. To investigate the role of annexin 6 in intact cardiomyocytes, we used mice containing a targeted disruption of the annexin 6 gene. Compared with controls, the myocytes of annexin 6 null-mutant mice demonstrated a significant increase in the rates of shortening and relengthening. Intracellular Ca2+ transients in fura-2-loaded cardiomyocytes induced by caffeine showed a normal baseline and amplitude, whereas the rate of decay was doubled in annexin 6-/- myocytes compared with control mice. These results show that annexin 6 knockout in the mouse leads to an increase in myocyte contractility and faster diastolic Ca2+ removal from the cytoplasm. In light of published findings showing annexin 6 to be down-regulated in end-stage heart failure, these results are consistent with a role for annexin 6 as a negative inotropic factor in the regulation of cardiomyocyte mechanics.

Journal article

Chaudhri B, Hajjar RJ, Harding SE, Terracciano CMNet al., 2001, Effects of over-expression of SERCA2a on action potential duration, Ca<SUP>2+</SUP> entry and sarcoplasmic reticulum Ca<SUP>2+</SUP> content in rabbit ventricular myocytes, Scientific Meeting of the Physiological-Society, Publisher: WILEY, Pages: 74P-74P, ISSN: 0022-3751

Conference paper

Sarkar D, Vallance P, Harding SE, 2001, Nitric oxide: not just a negative inotrope, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 3, Pages: 527-534, ISSN: 1388-9842

Journal article

Watt DJ, Goldring K, Harding SE, Fuller S, Sun H, Naunton-Morgan Net al., 2001, A preliminary study on the effect of galectin-1 on cardiomyocytes, NEUROMUSCULAR DISORDERS, Vol: 11, Pages: 651-651, ISSN: 0960-8966

Journal article

Shevchuk AI, Gorelik J, Harding SE, Lab MJ, Klenerman D, Korchev YEet al., 2001, Simultaneous measurement of Ca<SUP>2+</SUP> and cellular dynamics:: Combined scanning ion conductance and optical microscopy to study contracting cardiac myocytes, BIOPHYSICAL JOURNAL, Vol: 81, Pages: 1759-1764, ISSN: 0006-3495

Journal article

del Monte F, Hajjar RJ, Harding SE, 2001, Overwhelming evidence of the beneficial effects of SERCA gene transfer in heart failure, CIRCULATION RESEARCH, Vol: 88, Pages: E66-E66, ISSN: 0009-7330

Journal article

Davia K, Bernobich E, Ranu HK, del Monte F, Terracciano CMN, MacLeod KT, Adamson DL, Chaudhri B, Hajjar RJ, Harding SEet al., 2001, SERCA2a overexpression decreases the incidence of aftercontractions in adult rabbit ventricular myocytes, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 33, Pages: 1005-1015, ISSN: 0022-2828

Journal article

Heubach JF, Graf EM, Molenaar P, Jäger A, Schröder F, Herzig S, Harding SE, Ravens Uet al., 2001, Murine ventricular L-type Ca<SUP>2+</SUP> current is enhanced by zinterol <i>via</i> β<sub>1</sub>-adrenoceptors, and is reduced in TG4 mice overexpressing the human β<sub>2</sub>-adrenoceptor, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 133, Pages: 73-82, ISSN: 0007-1188

Journal article

Sarkar D, Vallance P, Amirmansour C, Harding SEet al., 2000, Positive inotropic effects of NO donors in isolated guinea-pig and human cardiomyocytes independent of NO species and cyclic nucleotides, CARDIOVASCULAR RESEARCH, Vol: 48, Pages: 430-439, ISSN: 0008-6363

Journal article

Vaughn DW, 2000, Invited commentary: Dengue lessons from Cuba, AMERICAN JOURNAL OF EPIDEMIOLOGY, Vol: 152, Pages: 800-803, ISSN: 0002-9262

Journal article

Gong HB, Adamson DL, Ranu HK, Koch WJ, Heubach JF, Ravens U, Zolk O, Harding SEet al., 2000, The effect of Gi-protein inactivation on basal, and β<sub>1</sub>- and β<sub>2</sub>AR-stimulated contraction of myocytes from transgenic mice overexpressing the β<sub>2</sub>-adrenoceptor, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 131, Pages: 594-600, ISSN: 0007-1188

Journal article

Yokoyama H, Gunasegaram S, Harding SE, Avkiran Met al., 2000, Sarcolemmal Na<SUP>+</SUP>/H<SUP>+</SUP> exchanger activity and expression in human ventricular myocardium, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 36, Pages: 534-+, ISSN: 0735-1097

Journal article

Adamson DL, Money-Kyrle ARW, Harding SE, 2000, Functional evidence for a cyclic-AMP related mechanism of action of the β<sub>2</sub>-adrenoceptor in human ventricular myocytes, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 32, Pages: 1353-1360, ISSN: 0022-2828

Journal article

Ranu HK, Mak JCW, Barnes PJ, Harding SEet al., 2000, G<sub>i</sub>-dependent suppression of β<sub>1</sub>-adrenoceptor effects in ventricular myocytes from NE-treated guinea pigs, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 278, Pages: H1807-H1814, ISSN: 0363-6135

Journal article

Adamson DL, Harding SE, 2000, Rp-cAMPS has no effect on adenosine A<sub>1</sub> receptors in guinea-pig cardiomyocytes, BASIC RESEARCH IN CARDIOLOGY, Vol: 95, Pages: 114-118, ISSN: 0300-8428

Journal article

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