Monovalent cation (MC) current in cardiac and smooth muscle cells: regulation by intracellular Mg2+ and inhibition by polycations.
1 Previously we have described a monovalent cation (MC) current that could be unmasked by the removal of extracellular divalent cations in vascular smooth muscle cells (SMC) and cardiac myocytes, but specific and potent inhibitors of MC current have not been found, and the mechanism of its intracellular regulation remains obscure. 2 Here we show that small MC current is present in intact cells and could be dramatically up-regulated during cell dialysis. MC current in dialyzed cells strongly resembled monovalent cation current attributed to Ca(2+) release-activated Ca(2+)-selective (CRAC) channels, but its activation did not require depletion of Ca(2+) stores, and was observed when the cells were dialyzed with, or without BAPTA. 3 Intracellular free Mg(2+) inhibits MC current with K(d)=250 microM. 4 Extracellular (but not intracellular) spermine effectively blocked MC current with K(d) =3-10 microM, while store-operated cations (SOC) channels and capacitative Ca(2+) influx were not affected. 5 Spermine effectively inhibited MC current-induced SMC depolarization, and prevented Ca(2+) paradox-induced vascular contracture. 6 Both, MC and SOC currents were inhibited by 2-aminoethoxydiphenyl borate (2-APB). 7 It is concluded that MC current could be regulated by intracellular Mg(2+), and low concentrations of extracellular spermine could be used to discriminate it from SOC current, and to assess its role in cellular function.
Zakharov
Sergey I
SI
Vascular Biology Unit, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, U.S.A.
Smani
Tarik
T
Leno
Endri
E
Macianskiene
Regina
R
Mubagwa
Kanigula
K
Bolotina
Victoria M
VM
D000818:Animals; D002414:Cations, Monovalent / Q000378:metabolism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008274:Magnesium / Q000502:physiology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology*; D000071228:Polyelectrolytes; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D002414:Cations, Monovalent; D007473:Ion Channels; D008274:Magnesium; D011073:Polyamines; D000071228:Polyelectrolytes