Small cerebral arteries actively constrict when pressurised and this 'myogenic response' seems, as the name suggests, to be a property of the muscle insofar as it persists in the absence of the endothelium and does not appear to rely on the release of any identified transmitter or vasoactive substance. A striking feature of the myogenic response is a pressure-related depolarisation of the vascular smooth muscle (vsm) cells. The membrane potential of vsm cells in non-pressurised [rat cerebral] vessels is about -70 mV and this value falls to about -30 mV at 100 mmHg. This depolarisation, which persists for as long as the vessel is pressurised, will increase the open probability (Popen) of voltage gated ion channels. It is thought that such an increase in the Popen of dihyropyridine- (DHP) sensitive calcium channels promotes Ca2+ entry and supports a Ca2+ - and DHP-sensitive contraction. Methods and Rationale The membrane conductance changes that must underlie such a marked depolarisation are not known and it is unlikely that conventional voltage clamp techniques will be able to address this problem because of the extreme technical difficulty of recording from small cells in a delicate pressurised vessel. Using the self-referencing, ion-selective vibrating microelectrode (seris-electrode - developed at the BRC) in combination with Halpern pressure-myography, it may be possible to detect, as changes in the concentration of various ions close to the surface of these vessels occurs, the activity of those channels, exchangers and pumps that are influenced by pressure and which may participate in the myogenic depolarisation. This technique offers the opportunity to investigate the changes in transmembrane flux of Ca 2+, Cl-, K+, Na+ & H+ that occur as these rat small cerebral vessels are pressurised. Preliminary data gathered during a short visit to the BRC during June and July 1997 demonstrated that the seris-electrode can indeed detect changes in both Ca2+ and Cl-concentration close to pressurised arteries. In both cases the seris-electrode detected higher concentrations close to the vessel suggesting an overall efflux of these ions. The magnitude of the efflux was sensitive to transmural pressure changes at 37o C but not at room temperature. (It is interesting and potentially useful feature of the myogenic response to pressure is that it is absent below about 30o C.) In other experiments, where the effects of K+-induced depolarisation and DHP agonists and antagonists were tested, the changes in efflux detected by the seris-electrode where consistent with the idea that both Cl-and Ca2+ conductances are increased during myogenic activation. Data gathered during this visit will provide a solid basis for a grant proposal to extend these investigations using the seris-electrode. Independent funding is being sought to establish this technique in the UK.
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