Extracellular Mg2+ inhibits receptor-mediated Ca(2+)-permeable non-selective cation currents in aortic smooth muscle cells.
The effects of extracellular Mg2+ on receptor-mediated Ca(2+)-permeable non-selective cation currents were investigated in a cultured aortic smooth muscle cell line (A7r5) from rat thoracic aorta, using the whole-cell voltage-clamp technique. Under the Cs(+)-containing internal solution, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward current with a high noise level. The reversal potential of these agonists-induced current was approximately +0 mV, and was not significantly altered by the replacement of [Cl-]i or [Cl-]o, suggesting that the inward current was a cation-selective channel. La3+ and Cd2+ (1 mM) almost completely abolished the vasopressin or endothelin-induced non-selective cation current; however, nifedipine (10 microM) failed to inhibit it significantly. Extracellular Mg2+ (3-20 mM) also markedly inhibited the vasopressin- or endothelin-induced non-selective cation current in a concentration-dependent manner. When a non-hydrolysable GTP-analogue, GTP gamma S (1 mM), was applied from the patch pipette, the non-selective cation current was gradually activated even in the absence of agonist (vasopressin or endothelin-1), probably due to the direct activation of GTP-binding proteins coupled to the receptors. Extracellular Mg2+ (3-20 mM) also suppressed the activation of non-selective cation current induced by GTP gamma S, suggesting that the inhibitory sites of Mg2+ are not located on the receptors. These results suggest that extracellular Mg2+ inhibits receptor-mediated non-selective cation current, which may contribute to the relaxation effects of Mg2+ in vascular smooth muscle cells.
Nakajima
T
T
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Iwasawa
K
K
Hazama
H
H
Asano
M
M
Okuda
Y
Y
Omata
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D019332:Endothelin-1 / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism
D015220:Calcium Channels; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008274:Magnesium