DIFFERENT ELECTRICAL RESPONSES TO VASOACTIVE AGONISTS IN MORPHOLOGICALLY DISTINCT SMOOTH-MUSCLE CELL-TYPES

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.