Blood supplies nutrients and metabolites to tissues, and also collects back the waste products that they produce through a system of exchange mediated through interstitial fluid. This fluid occupies the spaces between the cells and acts as their immediate environment, and as a result of its intermediary function its composition continually changes. The lymphatic vessels and capillaries allow exchange between water and solutes across their walls and facilitate the formation of lymph, a clear fluid. As such, the lymphatic system is a network of conduits that carry lymph, and is part of a system that includes all of the structures dedicated to the circulation and production of lymphocytes.
Lymphatic vessels produce regular spontaneous contractions which serve to propel fluid from the intersititum back to the general circulation. These contractions are preceded by action potential complexes which initiate the phasic contractions and research has focused on determining the underlying ion channels and mechanisms involved in this activity and how it can be influenced by neurotransmitters and potentially by drugs.
This mechanism of action, showing the role of intrinsic contractions of the lymph ducts as the essential propulsion mechanism in mammals was first shown by ICBC’s Director, Professor Noel McHale. His contribution to this field is recognized around the world as underpinning the fundamentals of lymphatic physiology.
Further, research at the Smooth Muscle Research Centre has used a combination of intracellular microelectrode and patch clamp recordings to characterise the main ionic conductance present in lymphatic smooth muscle and examine the contribution of each current to the electrical and mechanical activity of lymphatic vessels.
We have shown that lymphatic smooth muscle shares a number of similarities with other smooth muscle, and also with cardiac muscle which is quite unexpected. As such, the cells possess fast sodium current and calcium (T-type) current as well as a hyperpolarisation activated current. The Centre was the first to characterise this hyperpolarisation current, which appears to play an important role in the modulation of the slow pacemaker potential observed with intracellular recordings, which may modulate the frequency of pumping. Of particular interest was the observation that this cesium sensitive current was only observed in approximately 5% of cells studied, suggesting that lymphatic smooth muscle consists of a heterogeneous population of cells. We are able to use immunohistochemistry to distinguish cells on a morphological basis as well as electrophysiological characterisation of the cells of interest. By taking this approach and characterising the main ion channels and their currents, we are able to model the action potential more closely and examine the effects of different stimuli including drugs, observing how they modulate spontaneous contractions within the vessels of the lymphatic system.
This approach has far reaching effects in the treatment of diseases.