Lymphatic vessels produce regular spontaneous contractions which serve to propel fluid from the interstitium back to the general circulation. These contractions are preceded by action potential complexes (see figure 1) which initiate the phasic contractions. Our research is currently focused on the ionic mechanisms underlying this activity and how these mechanisms are altered by neurotransmitters.

Using a combination of intracellular microelectrode and patch clamp recording we have managed to successfully characterise the main ionic conductances present in lymphatic smooth muscle and examine the contribution of each current to the electrical and mechanical activity of lymphatic vessels.
The table below provides some details on the main currents present in lymphatic smooth muscle.

Current Putative role Blocked by % of cells expressing current Reference Na-current Coordination of contraction 1 uM TTX >80%

hollywood.pdf

hollywood.pdf 433.81 kB L-current Modulation of contraction force 1 uM Nifedipine >90%   T-current Modulating pacemaker frequency 100 uM Nickel <5%   Cl current contributes to pacemaker activity and plateau of action potential 1 mM 9AC, 100 uM Niflumic Acid >70%

LymphCl-paper.pdf

LymphCl-paper.pdf 205.12 kB BK current inhibits upstoke of action potential and contributes to repolarisation 300 nM Iberiotoxin, 100 nM Penitrem A. 100%

CottonLymph.pdf

CottonLymph.pdf 729.10 kB Delayed rectifier Contributes to repolarisation 10 mM TEA & 4-AP 100%

CottonLymph.pdf

CottonLymph.pdf 729.10 kB Hyperpolarisation activated current (If) Contibutes to pacemaker potential 1 mM Caesium <5%

McCloskey.pdf

McCloskey.pdf 288.49 kB

Although it is obvious that lymphatic smooth muscle shares a number of similarities with other smooth muscles, it also shares some similarities with cardiac muscle. Hence, they possess a fast Na current and T current as well as a hyperpolarisation activated current. We have recently characterised this current and an example of the currents obtained is shown here.This current appears to play an important role in the modulation of the slow pacemaker potential observed with intracellular recordings and thus may modulate the frequency of pumping. Interesting, this Cs 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 currently using immunohistochemical techniques to test if these cells can be distinguished on a morpholgical basis as well as an electrophysiological basis.Having characterised the main currents present in lymphatic smooth muscle we are in a better position to begin modelling the action potential and examine how different stimuli modulate spontaneous contractions within these vessels.