Molecular cloning and characterization of the intermediate-conductance Ca2+-activated K+ channel in vascular smooth muscle - Relationship between K-Ca channel diversity and smooth muscle cell function
Cb. Neylon et al., Molecular cloning and characterization of the intermediate-conductance Ca2+-activated K+ channel in vascular smooth muscle - Relationship between K-Ca channel diversity and smooth muscle cell function, CIRCUL RES, 85(9), 1999, pp. E33-E43
Recent evidence suggests that functional diversity of vascular smooth muscl
e is produced in part by a differential expression of ion channels. The aim
of the present study was to examine the role of Ca2+-activated K+ channels
(K-Ca channels) in the expression of smooth muscle cell functional phenoty
pe. We found that smooth muscle cells exhibiting a contractile function exp
ress predominantly large-conductance (approximate to 200 pS) K-Ca (BK) chan
nels. In contrast, proliferative smooth muscle cells express predominantly
K-Ca channels exhibiting a much smaller conductance (approximate to 32 pS).
These channels are blocked by low concentrations of charybdotoxin (10 nmol
/L) but, unlike BK channels, are insensitive to iberiotoxin (100 nmol/L). T
o determine the molecular identity of this K+ channel, we cloned a 1.9-kb c
DNA from an immature-phenotype smooth muscle cell cDNA library. The cDNA co
ntains an open reading frame for a 425 amino acid protein exhibiting sequen
ce homology to other K-Ca channels, in particular with mIK1 and hIK1. Expre
ssion in oocytes gives rise to a K+-selective channel exhibiting intermedia
te-conductance (37 pS at -60 mV) and potent activation by Ca2+ (K-d 120 nmo
l/L), Thus, we have cloned and characterized the vascular smooth muscle int
ermediate-conductance K-Ca channel (SMIK), which is markedly upregulated in
proliferating smooth muscle cells. The differential expression of these K-
Ca channels in functionally distinct smooth muscle cell types suggests that
K-Ca channels play a role in defining the physiological properties of vasc
ular smooth muscle. The full text of this article is available at http://ww
w.circresaha.org.