title: The bestrophin- and TMEM16A-associated Ca(2+)- activated Cl(–) channels in vascular smooth muscles.
abstract: The presence of Ca(2+)-activated Cl(–) currents (I(Cl(Ca))) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca(2+)]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with I(Cl(Ca)). Two distinct I(Cl(Ca)) are characterized in VSMCs; the cGMP-dependent I(Cl(Ca)) dependent upon bestrophin expression and the ‘classical’ Ca(2+)-activated Cl(–) current, which is bestrophin-independent. Interestingly, TMEM16A is essential for both the cGMP-dependent and the classical I(Cl(Ca)). Furthermore, TMEM16A has a role in arterial contraction while bestrophins do not. TMEM16A’s role in the contractile response cannot be explained however only by a simple suppression of the depolarization by Cl(–) channels. It is suggested that TMEM16A expression modulates voltage-gated Ca(2+) influx in a voltage-independent manner and recent studies also demonstrate a complex role of TMEM16A in modulating other membrane proteins.
authors.forename: Vibeke Secher
authors.initials: VS
authors.lastname: Dam
authors.forename: Donna M B
authors.initials: DM
authors.lastname: Boedtkjer
authors.forename: Christian
authors.initials: C
authors.lastname: Aalkjaer
authors.forename: Vladimir
authors.initials: V
authors.lastname: Matchkov
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D018118:Chloride Channels; D005136:Eye Proteins