Christian Aalkjær

The contribution of potassium channels to human thoracic duct contractility

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In smooth muscle cells, potassium permeability is high and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by the smooth muscle cells of lymphatic vessels and it is likely that potassium channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct potassium channels to human lymphatic vessel contractility. Thoracic ducts were harvested from 43 patients and mounted in a wire myograph for isometric force measurements or membrane potential recordings with an intracellular microelectrode. Using potassium channel blockers and activators we demonstrate a functional contribution to human lymphatic vessel contractility from all the major classes of potassium channels; ATP-sensitive (KATP), Ca(2+)-activated, inward rectifier and voltage-dependent and those were confirmed at mRNA level. Contraction amplitude, frequency and baseline tension were altered depending on which channel was blocked or activated. Microelectrode impalements of lymphatic vessels determined an average resting membrane potential of -43.1±3.7mV. We observed that membrane potential changes <5mV could have large functional effects with contraction frequencies increasing three-fold. In general, KATP channels appeared to be constitutively open since incubation with glibenclamide increased contraction frequency in spontaneously active vessels and depolarized and initiated contractions in previously quiescent vessels. The largest change in membrane voltage was observed with the KATP opener pinacidil, which caused a 24±3mV hyperpolarization. We conclude that potassium channels are important modulators of human lymphatic contractility.

TidsskriftA J P: Heart and Circulatory Physiology (Online)
Sider (fra-til)H33-H43
Antal sider11
StatusUdgivet - 28 apr. 2014

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