| First Author | Wan E | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 5 | Pages | 1859-67 |
| PubMed ID | 23325318 | Mgi Jnum | J:197754 |
| Mgi Id | MGI:5494500 | Doi | 10.1096/fj.12-223511 |
| Citation | Wan E, et al. (2013) Reduced vascular smooth muscle BK channel current underlies heart failure-induced vasoconstriction in mice. FASEB J 27(5):1859-67 |
| abstractText | Excessively increased peripheral vasoconstriction is a hallmark of heart failure (HF). Here, we show that in mice with systolic HF post-myocardial infarction, the myogenic tone of third-order mesenteric resistance vessels is increased, the vascular smooth muscle (VSM) membrane potential is depolarized by ~20 mV, and vessel wall intracellular [Ca(2+)] is elevated relative to that in sham-operated control mice. Despite the increased [Ca(2+)], the frequency and amplitude of spontaneous transient outward currents (STOCs), mediated by large conductance, Ca(2+)-activated BK channels, were reduced by nearly 80% (P<0.01) and 25% (P<0.05), respectively, in HF. The expression of the BK alpha and beta1 subunits was reduced in HF mice compared to controls (65 and 82% lower, respectively, P<0.01). Consistent with the importance of a reduction in BK channel expression and function in mediating the HF-induced increase in myogenic tone are two further findings: a blunting of paxilline-induced increase in myogenic tone in HF mice compared to controls (0.9 vs. 10.9%, respectively), and that HF does not alter the increased myogenic tone of BK beta1-null mice. These findings identify electrical dysregulation within VSM, specifically the reduction of BK currents, as a key molecular mechanism sensitizing resistance vessels to pressure-induced vasoconstriction in systolic HF. |
