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Eur J Pharmacol. 2013 Dec 5;721(1-3):21-8. doi: 10.1016/j.ejphar.2013.09.060. Epub 2013 Oct 7.

Sarcoplasmic reticulum Ca(2+) refilling is determined by L-type Ca(2+) and store operated Ca(2+) channels in guinea pig airway smooth muscle.

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Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF, México.


Sarcoplasmic reticulum Ca(2+) refilling (SRREF) is crucial to sustain the agonists induced airway smooth muscle contraction. Nevertheless, its mechanisms have not been clearly described yet, although L-type voltage dependent, store operated, receptor operated channels and the Na(+)/Ca(2+) exchanger in its reverse mode (NCXREV) have been proposed as Ca(2+) handling proteins participating in this process. We found that in guinea pig and bovine tracheal smooth muscle, SRREF induced by caffeine was completely abolished by thapsigargin, even in the presence of Bay K8644, an activator of the L-type Ca(2+) channel. Activation of NCXREV in guinea pig tracheal myocytes increased SRREF in ~70%, while opening of the L-type Ca(2+) channels with Bay K8644 and favoring the capacitative Ca(2+) entry with 2-APB (32 μM) also augmented the SRREF by ~170% and ~71%, respectively. Methoxyverapamil (D-600, an L-type Ca(2+) channel blocker), 2-APB (100 µM, antagonist of the capacitative Ca(2+) entry) and PPADS (NCXREV blocker) diminished the SRREF by ~63%, ~72% and ~31%, respectively. The simultaneous addition of D-600 and 2-APB annulled SRREF. These last results were also seen when carbachol was used instead of caffeine. In tracheal rings, 2-APB and nifedipine abolished the carbachol-induced contraction. We concluded that the sarcoplasmic reticulum Ca(2+) pump is the only mechanism involved in the SRREF and that L-type Ca(2+) voltage dependent and store operated Ca(2+) channels are the principal membranal Ca(2+) handling proteins that provide extracellular Ca(2+) for SRREF and carbachol-induced contraction in the guinea pig airway smooth muscle; NCXREV seems to play a minor role.


Airway smooth muscle; L-type Ca(2+) channels; SERCA; Sarcoplasmic reticulum; Store operated Ca(2+) channels

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