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Professor Clive Orchard

Professor Clive Orchard

Professor Clive Orchard
BSc, PhD(Lond)

Professor

Area of research

Regulation of cardiac-contraction coupling

Office D2
Medical Sciences Building,
University Walk, Bristol BS8 1TD
(See a map)

+44 (0) 117 331 1436

Summary

My research is focused on cardiac excitation-contraction coupling and its regulation. Using a variety of techniques (for example voltage clamp, fluorescent ion indicators,whole cell and confocal microscopy, immunohistochemistry, RT-PCR and computer modelling) we are investigating how the rise of intracellular Ca 2+ that causes contraction is initiated, and how it is regulated by intracellular 2nd messenger pathways. A particular interest is the role of the t-tubules (invaginations of the surface membrane of cardiac ventricular myocytes) in this process. We have recently developed a technique that allows us to physically and functionally uncouple the t-tubules from the surface membrane, enabling us to investigate their function.

Using this technique we have been able to show that the t-tubules form a specialised region of the cell membrane for ion handling: many of the key proteins involved in excitation-contraction coupling are found predominantly at the t-tubules, and the regulation of these proteins appears to be better coupled to second messenger pathways at the t-tubules than at the surface membrane. This work not only helps our understanding of cardiac cell function, but may also be important in understanding heart failure, in which t-tubule density decreases and ion channel expression and regulation are altered. We are also interested in how a variety of physiological and pathophysiological interventions, such as beta adrenergic stimulation and acidosis, alter excitation - contraction coupling and hence cardiac cell function.

Activities / Findings

 

  • Tonic phosphorylation by PKA- and CamKII-dependent phosphorylation of L-type Ca2+ channels, which are localised at t-tubules, maintains ICa
  • Ca2+ efflux from the sarcoplasmic reticulum via the Ca2+ ATPase occurs only at t-tubules  
  • Inhibition of either the NCX or SERCA blocked both spontaneous Ca2+ transients and action potentials in the AVN pacemaker 

Skills

  • arrhythmia
  • hypertension

Methodologies

  • Molecular Biology
  • PCR
  • Ca2+ imaging
  • Immunocytochemistry
  • Immunohistochemistry
  • Electrophysiological recording

Memberships

Organisations

School of Physiology and Pharmacology

Other sites

Research Areas

Selected publications

Read more >

Recent publications

View complete publications list in the University of Bristol publications system

Networks & contacts

  • Jules Hancox - Bristol
  • Andrew James - Bristol

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