Electrophysiological Properties of Rat Mesenteric Lymphatic Vessels and their Regulation by Stretch

Abstract

Background: In mammals, lymph is propelled centrally primarily via the phasic contractions of collecting lymphatic vessels, known as lymphatic pumping. Electrophysiological studies conducted in guinea pig and sheep mesenteric lymphatic vessels indicate that contractions are initiated in the lymphatic muscle by nifedipine-sensitive action potentials (APs). Lymphatic pumping is highly sensitive to luminal fluid loading and the mechanical properties of this stretch-induced pumping have been consistently studied, in particular in rat mesenteric lymphatic vessels. However, membrane potential (Vm) and the electrophysiological events underlying stretch-induced lymphatic pumping have not been investigated in the rat. The aim of this study was thus to examine the properties of rat mesenteric lymphatic muscle Vm under resting conditions and to assess changes in Vm caused by distension. Methods and Results: Lymphatic muscle Vm was measured with sharp intracellular microelectrodes either in unstretched conditions or under isometric tension provided by a wire-myograph. In unstretched vessels, Vm was -48 -2 mV (n = 30). APs (amplitude *25 mV) were observed at a frequency of *8/min and were abolished by nifedipine. Under isometric tension, Vm was less polarized (-36 -1 mV, n = 23), even at minimum tension. Increase in tension led to increase in contraction strength and contraction/AP frequency, while Vm was slightly hyperpolarized and AP amplitude not markedly altered. Conclusions: In our experimental conditions, rat lymphatic muscle has electrophysiological characteristics similar to that in other species. It responds to an increase in isometric tension with an increase in AP frequency, but resting Vm is not significantly affected.

Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca2+] in Rat Mesenteric Lymphatic Vessels

“…31,32 Ca 2 + movement via the L-type channels has been thought to contribute significantly to the regulation of lymphatic pump activity, while intracellular Ca 2 + flux plays a less significant role that may be modified by transmural pressure. 16,17 Our observations confirm that sarcolemmal Ca 2 + entry via L-type Ca 2 + channels contributes to the spontaneous Ca 2 + transients that precede lymphatic phasic contractions. Studies on mesenteric lymphatic vessels using wire myograph have shown that nifedipine in rats (10 -6 M) 16 and in humans (3 · 10 -9 M) 33 abolishes lymphatic pumping.…”

“…16,17 Our observations confirm that sarcolemmal Ca 2 + entry via L-type Ca 2 + channels contributes to the spontaneous Ca 2 + transients that precede lymphatic phasic contractions. Studies on mesenteric lymphatic vessels using wire myograph have shown that nifedipine in rats (10 -6 M) 16 and in humans (3 · 10 -9 M) 33 abolishes lymphatic pumping. Our findings with the lymphatic vessels isolated from rats that did not receive alcohol reflect the results of Atchison and Johnston, who used isolated bovine mesenteric lymphatic vessels and observed that nifedipine, applied at the same concentration we used, decreased both contraction frequency and amplitude of contraction.…”

“…Calcium transport across the sarcolemma via L-type channel contributes significantly to the contractile activity of collecting lymphatics. 16,17 Moreover, modulation of Ca 2 + release from intracellular stores has been suggested to be involved in the pressure-induced enhancement of lymphatic contractions. 18 Pace-making in lymphatic vessels is not generated by a single current, but relies on complex interactions between multiple Ca 2 + currents.…”

The Integrative Five-Fluid Circulation System in the Human Body

“…There is evidence that the lymphatic muscle cells are originated from mesenchymal progenitors [97]. There is also evidence that electrical action potentials trigger lymphatic smooth muscle contractions and vice versa [98]. In fact, the spontaneous and intrinsic nature/origin of these contractions suggests that each action potential/(rhythmic contraction) is preceded by a pacemaker event, like cardiac contraction (see Figure 2 of [96]).…”

Constitutively Enhanced Lymphatic Pumping in the Upper Limbs of Women Who Later Develop Breast Cancer-Related Lymphedema

“…Lymphatic drainage involves active contractile pumping, both in animal models [9][10][11][12] and human limbs. 13 To assess lymphatic collector vessel pump function in the upper limbs of women with established BCRL, pump function was quantified as the maximum pressure (Ppump) generated in the collector lymphatics when lymph flow was blocked by inflating a cuff around the upper arm (lymphatic congestion lymphoscintigraphy 14 )…”