Disorganization by calcium antagonists of actin microfilament in aortic smooth muscle cells.
To assess the physiological role of intracellular Ca2+ in the organization of actin microfilaments in smooth muscle cells, we employed several types of Ca2+ antagonists. The rabbit aortic smooth muscle cells treated with the putative intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB 8) at 5-100 microM showed a loss or a decrease in size and length of the actin-containing microfilament structure in a dose-dependent manner. Similar disorganization of actin structure was observed in the smooth muscle cells treated with 1-(5-isoquinolinesulfonyl)-homopiperazine (HA 1077) at 5-100 microM, which is a new type of Ca2+ antagonist different from Ca2+ entry blocker. In contrast, 100 microM verapamil and diltiazem induced no reorganization of the actin microfilament structure. Antimycin A decreased the ATP levels in smooth muscle cells and disorganized the actin-containing structure. Unlike antimycin A, TMB 8 and HA 1077 did not lower the ATP level below the threshold needed to maintain the actin filament structure. Both TMB 8 and HA 1077 directly interacted with neither the actin monomer nor F-actin in a viscometrical assay system. Thus these reagents may induce the disorganization of actin microfilament structure in smooth muscle cells through the indirect reaction(s) with the actin, suggesting that an appropriate level of ATP and Ca2+ and/or its involving reactions may be essential for maintenance of the actin structure.
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D011817:Rabbits; D014665:Vasodilator Agents
D000199:Actins; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate