Molecular determinants of voltage-gated potassium currents in vascular smooth muscle

Abstract

Voltage-gated K+ channels (Kv) play an important role in regulating contraction of vascular smooth muscle cells (VSMC) through their effects on membrane potential and on voltage-gated Ca2+ channel activity. Kv channels are tetrameric structures consisting of four identical or closely related pore-forming alpha subunits that may be associated with accessory subunits. More than 30 different gene products that contribute to Kv channel complexes have been identified to date, some of which are subject to alternative splicing. Consequently, there is an enormous potential diversity in the molecular composition and properties of possible Kv channel complexes. Electrophysiologic measurements of K+ currents in VSMC suggest the presence of multiple Kv channel assemblies including: (1) rapidly inactivating, 4-aminopyridine-sensitive, (2) slowly inactivating, tetraethylammonium-insensitive, and (3) noninactivating, tetraethylammonium-sensitive components. Based on electro physiological and expression studies, it is likely that the latter two components are represented by a heteromultimeric complex of Kv1.2 with either Kv1.4 or Kv1.5 and a Kvbeta1 subunit, and by at least Kv2.1, respectively. The identity of the first A-type current component, however, is not clear at this time. The relative abundance of these current components appears to vary in VSMC from different anatomical sites, from animals of different ages, and perhaps in VSMC within specific vascular segments. Expression of numerous Kv alpha and beta subunits has been demonstrated in VSMC at both the gene and protein level. However, the number of expressed subunits appears to be much larger than the number of apparent Kv current components. It remains unclear if all of these transcripts are expressed in VSMC or in other cell types in the tissue, or if expression patterns are homogenous or heterogeneous in VSMC at a given site.