What question did this study set out to answer?

To characterize the pharmacological and biophysical properties of nifedipine-insensitive, high voltage-activated Ca2+ currents (NICCs) in rat mesenteric terminal arteries and compare them to cloned alpha1E and alpha1G channels.

October 1, 2002British Journal of PharmacologyOpen Access

T‐channel‐like pharmacological properties of highvoltage‐activated, nifedipine‐insensitive Ca²⁺ currents inthe rat terminal mesenteric artery

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Authors

HMHiromitsu MoritaFukuoka Dental College JSJuan ShiSichuan University YIYushi ItoKurume University

Discussion

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Implication

Electrophysiological study demonstrates T-type channel blocker sensitivity in high-voltage-activated calcium currents in rat mesenteric arteries, suggesting distinct channel pharmacology.

Key Points

To characterize the pharmacological and biophysical properties of nifedipine-insensitive, high voltage-activated Ca2+ currents (NICCs) in rat mesenteric terminal arteries and compare them to cloned alpha1E and alpha1G channels.
Applied whole-cell patch-clamp techniques using 10 mM Ba2+ as the charge carrier on isolated rat mesenteric terminal arteries and heterologously expressed alpha1E (in BHK cells) and alpha1G (in HEK293 cells).
Assessed channel inhibition by administering high-voltage-activated channel toxins (SNX-482, sFTX3.3, omega-conotoxin GVIA, omega-agatoxin IVA) and classical T-type channel blockers (mibefradil, nimodipine, phenytoin, ethosuximide, SUN N5030).
Rat NICCs were insensitive to toxins including SNX-482 and sFTX3.3 (which inhibited alpha1E by 82% at 200 nM with an IC50 of 11.1 nM and alpha1G by 20% at 1 microM, respectively), while nimodipine suppressed NICC, alpha1E, and alpha1G currents by 40%, 3%, and 85%, respectively.
Mibefradil inhibited rat NICC and alpha1G currents voltage-dependently with comparable potencies, yielding IC50 values of 3.5 microM versus 0.3 microM at -100 mV and 2.4 microM versus 0.14 microM at -60 mV.
T-type channel blockers phenytoin (22% inhibition at 100 microM), ethosuximide (IC50 of 27.8 mM), and SUN N5030 (IC50 of 0.53 microM for NICC versus 0.32 microM for alpha1G at -60 mV) demonstrated strong inhibitory profiles against NICCs.

Cite This Study

Morita et al. (2002) studied this question.

synapsesocial.com/papers/6a7c04dfae178dbf17c6544b https://doi.org/10.1038/sj.bjp.0704892

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Implication

Electrophysiological study demonstrates T-type channel blocker sensitivity in high-voltage-activated calcium currents in rat mesenteric arteries, suggesting distinct channel pharmacology.

T‐channel‐like pharmacological properties of highvoltage‐activated, nifedipine‐insensitive Ca²⁺ currents inthe rat terminal mesenteric artery

Discussion

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Implication

Key Points

Cite This Study

T‐channel‐like pharmacological properties of highvoltage‐activated, nifedipine‐insensitive Ca²⁺ currents inthe rat terminal mesenteric artery

Discussion

Member takes

Implication

Key Points

Cite This Study

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