Biomedical subjects

Theodor Burdyga

Publications and source records attributed to Theodor Burdyga.

3 recordsLinked to original sources

PubMed2003

Force and myosin light chain phosphorylation in dog airway smooth muscle activated in different ways.

To assess activation mechanisms of dog trachealis muscle and test whether isometric force generation could be separated from myosin light-chain (MLC) phosphorylation, force and phosphorylation were measured in the presence of wortmannin (a light-chain kinase inhibitor) or Y-27632 (a rho-kinase inhibitor) during electrically stimulated tetani and sustained contractures induced by acetylcholine, KCl, or calyculin A, a light-chain phosphatase inhibitor which caused irreversible contractures and both di- and mono-phosphorylation of light chain. Phosphorylation was not much more than half under any circumstances. A nearly constant proportionality between steady force and phosphorylation existed over a 9-fold force range during contractures and 25-sec tetani, except that force correlated best with the di-phosphorylated light chain produced by calyculin A. Phosphorylation was disproportionately higher than force at the outset of tetani, and this disproportion was exaggerated by Y-27632. The results suggest that about half the light chain is sequestered from kinases and that mechanical activation is tightly linked to phosphorylation, except at the outset of stimulation.

Acetylcholine↗

PubMed2002

Sarcoplasmic reticulum function and contractile consequences in ureteric smooth muscles.

This paper discusses the role of Ca2+-induced Ca2+ release (CICR) and inositol-1,4,5-trisphosphate (InsP3)-induced Ca2+ release (IICR) from the sarcoplasmic reticulum (SR) in the control of contractile activity in the ureter. The Ca2+ store in guinea-pig ureter has been found to be exclusively a CICR type with ryanodine receptors (RyRs) present. In the rat ureter the SR store is exclusively an IICR type with InsP3 receptors (InsP3Rs) present. Guinea-pig ureteric cells in vitro and in situ have been found to generate Ca2+ sparks--small localized, transient releases from RyRs. The sparks are enhanced by caffeine and blocked by emptying the SR. In rat cells Ca2+ puffs occur in response to agonists, representing the opening of InsP3Rs. The puffs can be abolished by heparin or store emptying. These SR Ca2+-release events affect the excitability of the ureteric cells. In guinea-pig cells, spontaneous transient outward currents (STOCs) can be recorded in response to caffeine application (an agonist for RyR), followed by a shortening of the plateau phase of the action potential. This in turn causes a decrease in the amplitude and duration of the contractions of the ureter. If the SR is inhibited then STOCs are abolished, the action potential plateau prolonged and force increased. Thus it is concluded that the SR acts to limit contraction in the guinea-pig ureter. The mechanism underlying this involves its Ca2+ release being directed to Ca2+-activated K+ channels on the surface membrane and causing STOCs and hyperpolarization, and controlling the duration of the action potential. In rat ureter IICR acts to potentiate force via membrane depolarization and increased L-type Ca2+ entry into the cells. Thus the SR can alter cell signalling and excitation-contraction coupling in the ureter, but its precise role is species dependent. The ureter, with its species-dependent expression of either IICR or CICR provides an ideal system (a natural transgenic model) for studying the SR. Eventually, we will be able to apply this knowledge to the human ureter, to increase our understanding of its functioning in health and disease.

Action Potentials↗

PubMedDate not supplied

Calcium signalling in smooth muscle.

Calcium signalling in smooth muscles is complex, but our understanding of it has increased markedly in recent years. Thus, progress has been made in relating global Ca2+ signals to changes in force in smooth muscles and understanding the biochemical and molecular mechanisms involved in Ca2+ sensitization, i.e. altering the relation between Ca2+ and force. Attention is now focussed more on the role of the internal Ca2+ store, the sarcoplasmic reticulum (SR), global Ca2+ signals and control of excitability. Modern imaging techniques have shown the elaborate SR network in smooth muscles, along with the expression of IP3 and ryanodine receptors. The role and cross-talk between these two Ca(2+) release mechanisms, as well as possible compartmentalization of the SR Ca2+ store are discussed. The close proximity between SR and surface membrane has long been known but the details of this special region to Ca2+ signalling and the role of local sub-membrane Ca2+ concentrations and membrane microdomains are only now emerging. The activation of K+ and Cl- channels by local Ca2+ signals, can have profound effects on excitability and hence contraction. We examine the evidence for both Ca2+ sparks and puffs in controlling ion channel activity, as well as a fundamental role for Ca2+ sparks in governing the period of inexcitability in smooth muscle, i.e. the refractory period. Finally, the relation between different Ca2+ signals, e.g. sparks, waves and transients, to smooth muscle activity in health and disease is becoming clearer and will be discussed.

Animals↗