Angiotensin II-induced hypertension decreased the expression of the β1 subunit of the BK channel by approximately 65%, functionally uncoupling the channels from Ca2+ sparks and reducing their contribution to vascular tone.
Effect estimate: 65% less abundant
p-value: p=<0.05
Hypertension is a clinical syndrome characterized by increased vascular tone. However, the molecular mechanisms underlying vascular dysfunction during acquired hypertension remain unresolved. Localized intracellular Ca 2+ release events through ryanodine receptors (Ca2+ sparks) in the sarcoplasmic reticulum are tightly coupled to the activation of large-conductance, Ca2+-activated K+ (BK) channels to provide a hyperpolarizing influence that opposes vasoconstriction. In this study we tested the hypothesis that a reduction in Ca2+ spark-BK channel coupling underlies vascular smooth muscle dysfunction during acquired hypertension. We found that in hypertension, expression of the β1 subunit was decreased relative to the pore-forming α subunit of the BK channel. Consequently, the BK channels were functionally uncoupled from Ca2+ sparks. Consistent with this, the contribution of BK channels to vascular tone was reduced during hypertension. We conclude that downregulation of the β1 subunit of the BK channel contributes to vascular dysfunction in hypertension. These results support the novel concept that changes in BK channel subunit composition regulate arterial smooth muscle function.
Amberg et al. (2003) studied Hypertension. Angiotensin II-induced hypertension vs. Sham-operated normotensive controls was evaluated on Relative abundance of BK channel β1 transcripts (65% less abundant, p=<0.05). Angiotensin II-induced hypertension decreased the expression of the β1 subunit of the BK channel by approximately 65%, functionally uncoupling the channels from Ca2+ sparks and reducing their contribution to vascular tone.