MaxiK channels, Caveolin and Vascular Function

摘要

The large conductance, voltage- and Ca~(2+)-activated potassium (MaxiK, BK) channel and caveolin-1 play an important role in vascular function. MaxiK channels are composed of the pore-forming alpha- and modulatory beta-subunits. Caveolin-1 is a structural protein of caveolae, which are imaginations of the plasma membrane. Disruption of caveolae with beta-methylcyclodextrine impairs agonist-induced vascular contraction and MaxiK beta1 subunit gene ablation produces moderate hypertension. At the cellular level, MaxiK channels and caveolin-1 coexist. Immunolocalization demonstrates a striking proximity of both proteins and sucrose gradient centrifugation demonstrate that both caveolin and MaxiK alpha subunit commigrate to low-density fractions. Reverse co-im-munoprecipitation experiments indicate that both vascular caveolin-1 and MaxiK associate in a macromolecular complex. In vitro experiments indicate that in vascular smooth muscle MaxiK a subunit interacts directly with caveolin-1 via its carboxyl terminus. Interestingly, electrophysiological and immunocytochemistry experiments demonstrate that MaxiK a subunit surface targeting was dramatically prevented by caveolin-1 over-expression due to channel trapping in cytoplasmic compartments. Thus, caveolin-1 and MaxiK interaction favor their co-localization in caveolae, and possibly control MaxiK channel surface targeting in vascular smooth muscle. Supported by NIH (LT, ES) and AHA (ME and AA).