Cb. Neylon et al., DIFFERENT ELECTRICAL RESPONSES TO VASOACTIVE AGONISTS IN MORPHOLOGICALLY DISTINCT SMOOTH-MUSCLE CELL-TYPES, Circulation research, 75(4), 1994, pp. 733-741
Vascular smooth muscle cells (SMCs) in the blood vessel wall are frequ
ently heterogeneous in nature, differing in their gross morphology, si
ze, and shape, subcellular organelles, cytoskeleton, and contractile p
rotein composition. In adult rat arterial vessels, two populations of
SMCs have been shown to predominate: elongated bipolar cells, represen
ting the majority of cells, and epithelial-like SMCs. We examined the
ionic responses of these two types of SMCs, isolated by multiple subcu
lture, to vasoactive stimuli. Elevations in intracellular Na+ and Ca2 were measured with SBFI and fura 2, respectively, and changes in memb
rane potential were measured using the potential-sensitive fluorescent
probe bis-oxonol. The resting membrane potential of the elongated bip
olar cells was less negative than that of the epithelial-like SMCs. Ex
posure of the elongated SMCs to endothelin 1, alpha-thrombin, or argin
ine vasopressin induced elevations in [Ca2+](i) and [Na+](i) and membr
ane depolarization. Depolarization occurred because of entry of both N
a+ and Ca2+, and pharmacological blockade of Cl- or K+ channels did no
t attenuate the depolarization. In contrast, when [Ca2+](i) was elevat
ed by the same agonists in the epithelial-like SMCs there was a pronou
nced hyperpolarization that appeared to be the consequence of enhanced
activity of charybdotoxin-sensitive Ca2+-activated K+ channels becaus
e it was abolished by charybdotoxin (20 nmol/L), partially attenuated
by tetraethylammonium chloride (10 mmol/L), and unaffected by apamin (
1 mu mol/L), glibenclamide (1 mu mol/L), or 4-aminopyridine (5 mmol/L)
. Chelation of [Ca2+]i also abolished the hyperpolarization; instead,
a small depolarization was observed. We conclude that SMCs that exhibi
t different morphological characteristics can also differ with respect
to the ability of vasoactive agonists to activate Ca2+-activated K+ c
hannels. It is suggested that redistributions in SMC populations in pr
oliferative vascular diseases may alter the responsiveness of vessels
to vasoactive stimuli via cell type-specific modulation of specific me
mbrane ion channels.