Article date: October 2002
By: Hiromitsu Morita, Juan Shi, Yushi Ito, Ryuji Inoue in Volume 137, Issue 4, pages 467-476
Pharmacological properties of nifedipine‐insensitive, high voltage‐activated Ca2+ channels in rat mesenteric terminal arteries (NICCs) were investigated and compared with those of α1E and α1G heterologously expressed in BHK and HEK293 cells respectively, using the patch clamp technique.
With 10 mM Ba2+ as the charge carrier, rat NICCs (unitary conductance: 11.5 pS with 110 mM Ba2+) are almost identical to those previously identified in a similar region of guinea‐pig, such as in current‐voltage relationship, voltage dependence of activation and inactivation, and divalent cation permeability. However, these properties are considerably different when compared with α1E and α1G.
SNX‐482(200 nM and sFTX3.3 (1 μM), in addition to ω‐conotoxin GVIA (1 μM) and ω‐agatoxin IVA (100 nM), were totally ineffective for rat NICC currents, but significantly suppressed α1E (by 82% at 200 nM; IC50=11.1 nM) and α1G (by 20% at 1 μM) channel currents, respectively. A non‐specific T‐type Ca2+ channel blocker nimodipine (10 μM) differentially suppressed these three currents (by 40, 3 and 85% for rat NICC, α1E and α1G currents, respectively).
Mibefradil, the widely used T‐type channel blocker, almost equally inhibited rat NICC and α1G currents in a voltage‐dependent fashion with similar IC50 values (3.5 and 0.3 μM and 2.4 and 0.14 μM at −100 and −60 mV, respectively). Furthermore, other organic T‐type channel blockers such as phenytoin, ethosuximide, an arylpiperidine derivative SUN N5030 (IC50=0.32 μM at −60 mV for α1G) also exhibited comparable inhibitory efficacies for NICC currents (inhibited by 22% at 100 μM; IC50=27.8 mM; IC50=0.53 μM, respectively).
These results suggest that despite distinctive biophysical properties, the rat NICCs have indistinguishable pharmacological sensitivities to many organic blockers compared with T‐type Ca2+ channels.
Pharmacological properties of nifedipine‐insensitive, high voltage‐activated Ca2+ channels in rat mesenteric terminal arteries (NICCs) were investigated and compared with those of α1E and α1G heterologously expressed in BHK and HEK293 cells respectively, using the patch clamp technique.
With 10 mM Ba2+ as the charge carrier, rat NICCs (unitary conductance: 11.5 pS with 110 mM Ba2+) are almost identical to those previously identified in a similar region of guinea‐pig, such as in current‐voltage relationship, voltage dependence of activation and inactivation, and divalent cation permeability. However, these properties are considerably different when compared with α1E and α1G.
SNX‐482(200 nM and sFTX3.3 (1 μM), in addition to ω‐conotoxin GVIA (1 μM) and ω‐agatoxin IVA (100 nM), were totally ineffective for rat NICC currents, but significantly suppressed α1E (by 82% at 200 nM; IC50=11.1 nM) and α1G (by 20% at 1 μM) channel currents, respectively. A non‐specific T‐type Ca2+ channel blocker nimodipine (10 μM) differentially suppressed these three currents (by 40, 3 and 85% for rat NICC, α1E and α1G currents, respectively).
Mibefradil, the widely used T‐type channel blocker, almost equally inhibited rat NICC and α1G currents in a voltage‐dependent fashion with similar IC50 values (3.5 and 0.3 μM and 2.4 and 0.14 μM at −100 and −60 mV, respectively). Furthermore, other organic T‐type channel blockers such as phenytoin, ethosuximide, an arylpiperidine derivative SUN N5030 (IC50=0.32 μM at −60 mV for α1G) also exhibited comparable inhibitory efficacies for NICC currents (inhibited by 22% at 100 μM; IC50=27.8 mM; IC50=0.53 μM, respectively).
These results suggest that despite distinctive biophysical properties, the rat NICCs have indistinguishable pharmacological sensitivities to many organic blockers compared with T‐type Ca2+ channels.
British Journal of Pharmacology (2002) 137, 467–476. doi:10.1038/sj.bjp.0704892
DOI: 10.1038/sj.bjp.0704892
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