Different electrical responses to vasoactive agonists in morphologically distinct smooth muscle cell types.
Vascular smooth muscle cells (SMCs) in the blood vessel wall are frequently heterogeneous in nature, differing in their gross morphology, size, and shape, subcellular organelles, cytoskeleton, and contractile protein composition. In adult rat arterial vessels, two populations of SMCs have been shown to predominate: elongated bipolar cells, representing the majority of cells, and epithelial-like SMCs. We examined the ionic responses of these two types of SMCs, isolated by multiple subculture, to vasoactive stimuli. Elevations in intracellular Na+ and Ca2+ were measured with SBFI and fura 2, respectively, and changes in membrane potential were measured using the potential-sensitive fluorescent probe bis-oxonol. The resting membrane potential of the elongated bipolar cells was less negative than that of the epithelial-like SMCs. Exposure of the elongated SMCs to endothelin 1, alpha-thrombin, or arginine vasopressin induced elevations in [Ca2+]i and [Na+]i and membrane depolarization. Depolarization occurred because of entry of both Na+ and Ca2+, and pharmacological blockade of Cl- or K+ channels did not attenuate the depolarization. In contrast, when [Ca2+]i was elevated by the same agonists in the epithelial-like SMCs there was a pronounced hyperpolarization that appeared to be the consequence of enhanced activity of charybdotoxin-sensitive Ca(2+)-activated K+ channels because it was abolished by charybdotoxin (20 nmol/L), partially attenuated by tetraethylammonium chloride (10 mmol/L), and unaffected by apamin (1 mumol/L), glibenclamide (1 mumol/L), or 4-aminopyridine (5 mmol/L). Chelation of [Ca2+]i also abolished the hyperpolarization; instead, a small depolarization was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Neylon
C B
CB
Baker Medical Research Institute, Prahran, Victoria, Australia.
Avdonin
P V
PV
Dilley
R J
RJ
Larsen
M A
MA
Tkachuk
V A
VA
Bobik
A
A
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018999:Charybdotoxin; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology; D005453:Fluorescence; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D017540:Tunica Media / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D018118:Chloride Channels; D016232:Endothelins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D018999:Charybdotoxin; D019789:Tetraethylammonium; D012964:Sodium; D013917:Thrombin; D002118:Calcium