title: Monovalent cation and L-type Ca2+ channels participate in calcium paradox-like phenomenon in rabbit aortic smooth muscle cells.
abstract: 1. The effects of removal of extracellular divalent cations (experimental calcium paradox conditions) were studied on the whole-cell current in freshly isolated smooth muscle cells (SMCs), and on contraction in rabbit aortic rings. 2. Aortic rings treated for 30-60 min with extracellular Ca2+- and Mg2+-free solution contracted following readmission of extracellular Ca2+, even in the presence of nifedipine. 3. In isolated SMCs, the removal of extracellular Ca2+ and Mg2+ induced a non-inactivating whole-cell inward current and membrane depolarization. This current was a monovalent cation (MC) current which reversed at around 0 mV and conducted K+ >= Cs+ > Na+ > Li+. Extracellular divalent cations (Ca2+, Mg2+, Ba2+, Mn2+ and Ni2+) inhibited MC current. 4. Using noise analysis of the whole-cell MC current, the single MC channel conductance was estimated to be < 450 fS. 5. MC current was insensitive to nifedipine, TEA, 4-aminopyridine, SK&F 96365 and S-nitroso-N-acetyl-penicillamine (SNAP), but was decreased by amiloride and low pH. 6. When EGTA was present in Ca2+- and Mg2+-free solution, a significant nifedipine-sensitive Na+ current through L-type Ca2+ channels developed in addition to MC current. 7. It is concluded that upon the removal of extracellular Ca2+ and Mg2+ from resting SMCs, an inward MC current develops allowing Na+ influx and causing SMC depolarization which could be the important steps leading to vessel contraction upon Ca2+ readmission. Addition of EGTA to Ca2+- and Mg2+-free solution greatly potentiates Na+ influx and vessel contraction by allowing additional Na+ influx through L-type Ca2+ channels which are activated presumably by MC current-induced depolarization.
authors.affiliation: Vascular Biology Unit, Department of Medicine, Boston University Medical Center, Boston, MA 02118,, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Zakharov
authors.forename: D A
authors.initials: DA
authors.lastname: Mongayt
authors.forename: R A
authors.initials: RA
authors.lastname: Cohen
authors.forename: V M
authors.initials: VM
authors.lastname: Bolotina
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000166:cytology; D002118:Calcium / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002414:Cations, Monovalent / Q000493:pharmacokinetics; D002586:Cesium / Q000493:pharmacokinetics; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008094:Lithium / Q000493:pharmacokinetics; D008274:Magnesium / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000493:pharmacokinetics; D011817:Rabbits; D012964:Sodium / Q000493:pharmacokinetics; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002414:Cations, Monovalent; D002614:Chelating Agents; D007093:Imidazoles; C110881:S-nitro-N-acetylpenicillamine; D005973:Glutamine; D002586:Cesium; D004533:Egtazic Acid; D019789:Tetraethylammonium; D008094:Lithium; D012964:Sodium; D015761:4-Aminopyridine; D010396:Penicillamine; D008274:Magnesium; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D011188:Potassium; D002118:Calcium