Signal Transduction in Endothelium: Mechano-Sensing, Ion Channels and Intracellular Calcium

Re^3: symposium 377

Wolfgang Graier

On Thu Dec 10, Paul Fransen wrote
>On Thu Dec 10, Wolfgang Graier wrote
>>On Fri Dec 4, grover wrote
>>>Dr. Graier:  Fascinating results.  Hope you are having fun at the meeting. This model would require that ryanodine receptor containing SR, Na-Ca exchanger and eNOS all be in close proximity.  There have been suggestions that cavolae may contain all these components.  What is your opinion of these suggestions?
>>>Thank you very much for your mail. Yes, indeed, if our concept is true, Na/CaX, Ryanodine receptors and eNOS should be localized next to each other. Regarding the literature this should be in the cavaolae. However, ryanodine receptors have been reported throughout the whole cell while no accumulation was found in the subplasmalemmal region. Thus, I think, we need to clarify whether or not there are two ryanodine receptors with different distribution in the cells (with different function for e.g. eNOS activity and proliferation). In addition, we need to think on other proteins possible involved in this SCCU, which might be membrane bound IP3 receptors, channels and Ca-ATPase. Thus, although our data so far support the hypothesis very well, we need to focus to show exactly what you suggested: there must be an accumulation of Ca2+ regulatory proteins in context to superficial ER in the endothelium. Do you have data supporting or disquilifieing the SCCU concept?
>Is it possible that the elementary events of Ca-release (23 nM) described by Huser and Blatter (1997, AJP 273: C1775-1782) in vascular endothelial cells are part of the SCCU? They preceded the propagating calcium waves (increase of bulk concentration).
>Yes, I think they are. In fact I think localized Ca release is t he first event in an initiation of an Ca wave. However, so far our data indicate, Ca waves reflect somewhat an situation where the SCCU function is overcome by a strong Ca signal

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