cGMP reduces the sarcoplasmic reticulum Ca^sup 2+^ loading in airway smooth muscle cells: a putative mechanism in the regulation of Ca^sup 2+^ by cGMP

• Published in: Journal of muscle research and cell motility 2012-03, Vol.32 (6), p.375
• Main Author: Bazán-perkins, Blanca
• Format: Article
• Language: English
• ISSN: 0142-4319; 1573-2657
• DOI: 10.1007/s10974-011-9266-5

Ca^sup 2+^ and cGMP have opposite roles in many physiological processes likely due to a complex negative feedback regulation between them. Examples of opposite functions induced by Ca^sup 2+^ and cGMP are smooth muscle contraction and relaxation, respectively. A main Ca^sup 2+^ storage involved in contraction is sarcoplasmic reticulum (SR); nevertheless, the role of cGMP in the regulation of SR-Ca^sup 2+^ has not been completely understood. To evaluate this role, intracellular Ca^sup 2+^ concentration ([Ca^sup 2+^]i) was determinated by a ratiometric method in isolated myocytes from bovine trachea incubated with Fura-2/AM. The release of Ca^sup 2+^ from SR induced by caffeine was transient, whereas caffeine withdrawal was followed by a [Ca^sup 2+^]i undershoot. Caffeine-induced Ca^sup 2+^ transient peak and [Ca^sup 2+^]i undershoot after caffeine were reproducible in the same cell. Dibutyryl cGMP (db-cGMP) blocked the [Ca^sup 2+^]i undershoot and reduced the subsequent caffeine peak (SR-Ca^sup 2+^ loading). Both, the opening of SR channels with ryanodine (10 μM) and the blockade of SR-Ca^sup 2+^ ATPase with cyclopiazonic acid inhibited the [Ca^sup 2+^]i undershoot as well as the SR-Ca^sup 2+^ loading. The addition of db-cGMP to ryanodine (10 μM) incubated cells partially restored the SR-Ca^sup 2+^ loading. Cyclic GMP enhanced [Ca^sup 2+^]i undershoot induced by the blockade of ryanodine channels with 50 μM ryanodine. In conclusion, the reduction of SR-Ca^sup 2+^ content in airway smooth muscle induced by cGMP can be explained by the combination of SR-Ca^sup 2+^ loading and the simultaneous release of SR-Ca^sup 2+^. The reduction of SR-Ca^sup 2+^ content induced by cGMP might be a putative mechanism limiting releasable Ca^sup 2+^ in response to a particular stimulus.[PUBLICATION ABSTRACT]