| First Author | Rueda A | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 1 | Pages | e53321 |
| PubMed ID | 23301060 | Mgi Jnum | J:195818 |
| Mgi Id | MGI:5485324 | Doi | 10.1371/journal.pone.0053321 |
| Citation | Rueda A, et al. (2013) Abnormal Ca2+ spark/STOC coupling in cerebral artery smooth muscle cells of obese type 2 diabetic mice. PLoS One 8(1):e53321 |
| abstractText | Diabetes is a major risk factor for stroke. However, the molecular mechanisms involved in cerebral artery dysfunction found in the diabetic patients are not completely elucidated. In cerebral artery smooth muscle cells (CASMCs), spontaneous and local increases of intracellular Ca2+ due to the opening of ryanodine receptors (Ca2+ sparks) activate large conductance Ca2+-activated K+ (BK) channels that generate spontaneous transient outward currents (STOCs). STOCs have a key participation in the control of vascular myogenic tone and blood pressure. Our goal was to investigate whether alterations in Ca(2+) spark and STOC activities, measured by confocal microscopy and patch-clamp technique, respectively, occur in isolated CASMCs of an experimental model of type-2 diabetes (db/db mouse). We found that mean Ca(2+) spark amplitude, duration, size and rate-of-rise were significantly smaller in Fluo-3 loaded db/db compared to control CASMCs, with a subsequent decrease in the total amount of Ca(2+) released through Ca(2+) sparks in db/db CASMCs, though Ca(2+) spark frequency remained. Interestingly, the frequency of large-amplitude Ca(2+) sparks was also significantly reduced in db/db cells. In addition, the frequency and amplitude of STOCs were markedly reduced at all voltages tested (from -50 to 0 mV) in db/db CASMCs. The latter correlates with decreased BK channel beta1/alpha subunit ratio found in db/db vascular tissues. Taken together, Ca(2+) spark alterations lead to inappropriate BK channels activation in CASMCs of db/db mice and this condition is aggravated by the decrease in the BK beta1 subunit/alpha subunit ratio which underlies the significant reduction of Ca(2+) spark/STOC coupling in CASMCs of diabetic animals. |
