Acute regulation of tight junction ion selectivity in human airway epithelia

Abstract

Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La 3؉ movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na ؉ conductance, with a smaller increase in Cl ؊ conductance. The increase was mediated by histamine H1 receptors and depended on an increase in intracellular Ca 2؉ concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport.claudin ͉ histamine ͉ paracellular pathway

Effect of histamine on the electrophysiology of the human parietal pleura

“…H 1 receptors seem to play the most important role; in airway epithelia (Flynn et al 2009, Chan et al 1987, in vascular epithelia (Flynn et al 2009), in nostrils (Yang et al 2003), in Fallopian tubes and ovaries (Downing et al 1999(Downing et al , 2002 and in human colon (Keely et al 1995).…”

“…Histamine is considered to regulate ion transportation influencing mainly the paracellular pathway; it affects the tight junctions of adjacent cells and acutely increases the Na + conductance in airway epithelia (Flynn et al 2009, Hirace et al 2001, Zabner et al 2003. Conversely, histamine interferes with cellular transportation by regulating the ion transporters rather than altering the paracellular permeability and it increases electrical resistance of the human bronchial epithelial cells without increasing the permeability through the tight junctions, (Devalia et al 1994) an event which was also demonstrated in the porcine proximal colon cells (Ahrens et al 2003).…”

“…These effects are considered to be induced by histamines' interaction with its receptors, namely the H 1 and/or H 2 histamine receptors (Flynn et al 2009, Downing et al 1999.…”

“…Furthermore, it is now commonly demonstrated that histamine can acutely regulate trans-cellular transportation either via cellular transporters or via the paracellular pathway, influencing the tight junctions of adjacent cells in various epithelial tissues (Flynn et al 2009, Zabner et al 2003, Devalia et al 2004). The aforementioned effect of histamine is considered to be one of the underlining pathophysiologic mechanisms by which clinical manifestations appear following its release (Flynn et al 2009, Goldie andPedersen, 2005).…”

“…Histamine, following its release by the mast cells, regulates numerous functions in epithelial cells and is involved in the pathogenesis of many diseases (Flynn et al 2009). These effects are considered to be induced by histamines' interaction with its receptors, namely the H 1 and/or H 2 histamine receptors (Flynn et al 2009, Downing et al 1999.…”