KB-R7943 reveals possible involvement of Na(+)-Ca2+ exchanger in elevation of intracellular Ca2+ in rat carotid arterial myocytes.
A Na(+)/Ca(2+) exchanger (NCX) is one of the major regulators of intracellular Ca(2+) concentration ([Ca(2+)](i)) in cardiac muscle cells. Although vascular smooth muscle myocytes also express NCX proteins, their functional role has not been clear, mainly due to the lack of specific inhibitors of NCX and relatively low levels of expression of NCX. In the present study, we have examined the involvement of NCX in the Na(+) deficient (0 Na(+)) elevation of [Ca(2+)](i) in rat carotid arterial myocytes using KB-R7943, an inhibitor of NCX. Perfusion with a Na(+)-free bathing solution, prepared by replacement of Na(+) with N-methyl-D-glucamine, induced an elevation of [Ca(2+)](i), which was effectively inhibited by KB-R7943 (IC(50)=3.5 microM). This inhibition was reversed by washout of KB-R7943. In contrast, D600, a blocker of voltage dependent L-type Ca(2+) channels (VDCC), did not affect the 0 Na(+)-induced elevation of [Ca(2+)](i). Treatment of myocytes with ryanodine abolished the elevation of [Ca(2+)](i) caused by caffeine but not that caused by 0 Na(+). Application of Cd(2+), which is known to block NCX as well as VDCC, also significantly inhibited the 0 Na(+) induced elevation. These results suggest that KB-R7943 inhibits the extracellular Na(+) dependent ([Na(+)](o)) change in [Ca(2+)](i) in rat carotid arterial myocytes, which is presumably activated by the reverse mode of NCX.
Takai
Nobuhiko
N
Department of Molecular and Cellular Pharmacology, Nagoya City University, Japan.
Yamada
Aki
A
Muraki
Katsuhiko
K
Watanabe
Minoru
M
Imaizumi
Yuji
Y
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D019831:Sodium-Calcium Exchanger; D013890:Thiourea; D002118:Calcium