Abstract
TMEM16A, a Ca2+ activated Clchannel, is expressed in murine airway smooth muscle [1]. Deletion of TMEM16A in mice had little effect on initial contractions induced by cholinergic agonist [2]. Thus, we aimed to determine if TMEM16A is involved in sustained carbachol contractions in mouse bronchus. The effect of three TMEM16A inhibitors were studied on CCh-induced isometric contractions in rings from murine primary bronchi. CaCCinhA01 and benzbromarone had marked effects on the sustained component (10 min) of contractions, but were less effective at blocking the initial component. In contrast, Ani9 had little effect on CCh contractions. However, spontaneous transient inward currents in isolated bronchial smooth muscle cells were abolished on addition of Ani9, hence, it was an effective blocker of TMEM16A.
As CaCCinhA01 and benzbromarone may block L-type Ca2+ current, their effects were tested after addition of nifedipine. Both CaCCinhA01 and benzbromarone further reduced the CCh responses, suggesting both drugs have non-specific effects that cannot be accounted for by blocking L-type channels.
In conclusion, CaCCinhA01 and benzbromarone appear to be unsuitable for studying the role of TMEM16A in mouse ASM. In contrast, the effects of Ani9 suggests that TMEM16A has minor role in mediating CCh-induced contractions in this tissue.
As CaCCinhA01 and benzbromarone may block L-type Ca2+ current, their effects were tested after addition of nifedipine. Both CaCCinhA01 and benzbromarone further reduced the CCh responses, suggesting both drugs have non-specific effects that cannot be accounted for by blocking L-type channels.
In conclusion, CaCCinhA01 and benzbromarone appear to be unsuitable for studying the role of TMEM16A in mouse ASM. In contrast, the effects of Ani9 suggests that TMEM16A has minor role in mediating CCh-induced contractions in this tissue.
Original language | English |
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Pages (from-to) | 269-269 |
Number of pages | 1 |
Journal | Irish Journal of Medical Science |
Volume | 188 |
Issue number | SUPPL 10 |
DOIs | |
Publication status | Published - 22 Nov 2019 |