Abstract
Synthetic ion channels may have potential therapeutic applications, provided they possess appropriate biological activities. The present study was designed to examine the ability of small molecule-based synthetic Cl– channels to modulate airway smooth muscle responsiveness. Changes in isometric tension were measured in rat tracheal rings. Relaxations to the synthetic chloride channel SCC-1 were obtained during sustained contractions to KCl. The anion dependency of the effect of SCC-1 was evaluated by ion substitution experiments. The sensitivity to conventional Cl– transport inhibitors was also tested. SCC-1 caused concentration-dependent relaxations during sustained contractions to potassium chloride. This relaxing effect was dependent on the presence of extracellular Cl– and HCO3 −. It was insensitive to conventional Cl– channels/transport inhibitors that blocked the cystic fibrosis transmembrane conductance regulator and calcium-activated Cl– channels. SCC-1 did not inhibit contractions induced by carbachol, endothelin-1, 5-hydroxytryptamine or the calcium ionophore A23187. SCC-1 relaxes airway smooth muscle during contractions evoked by depolarizing solutions. The Cl– conductance conferred by this synthetic compound is distinct from the endogenous transport systems for chloride anions.
Highlights
Synthetic ion channels are of interest because of their potential therapeutic and research applications
The present study demonstrates that SCC-1 relaxes contractions of airway smooth muscle to high potassium in a Cl–dependent manner
Contractions elicited by carbachol, endothelin-1, 5-hydroxytryptamine and A23187 are not affected by the synthetic Cl– channel
Summary
Synthetic ion channels are of interest because of their potential therapeutic and research applications. Several synthetic ion channels have been synthesized and characterized [1,2,3,4], little information is available concerning their biological effects. A few studies have demonstrated the abilities of synthetic ion channels to kill bacteria [5,6,7,8] and to induce epithelial chloride (Cl–) secretion [9,10,11,12]. The action of synthetic ion channels on other biological systems, remains elusive. Previous studies have demonstrated the abilities of a small molecule-based synthetic Cl– channel assemblage [13] to alter membrane potential, the intracellular calcium concentration ([Ca2+]i) and the contraction level in cultured vascular smooth muscle cells [14]
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