Divalent metals differentially block cloned T-type calcium channels.
We tested divalent metals including Cu2+, Pb2+, and Zn2+ to determine their pharmacological profiles for blockade of cloned T-type Ca2+ channels (alpha1G, alpha1 H, and alpha1I). Effects of the metals were also evaluated for native low and high voltage-activated Ca2+ channels in rat sympathetic pelvic neurons. Cu2+ and Zn2+ blocked three T-type channel isoforms in a concentration-dependent manner with a higher affinity for alpha1H currents (IC50 = 0.9 microM and 2.3 microM). In pelvic neurons, only Zn2+ showed strong selectivity for T-type Ca2+ currents over high voltage-activated Ca2+ currents. Conversely, Pb2+ block on Ca2+ channels did not show distinctive selectivity. Taken together, these results suggest that besides Ni2+, Cu2+ and Zn2+ can be used as selective blockers of alpha1 H at low concentrations.
Jeong
Seong-Woo
SW
Department of Physiology, Yonsei University, Wonju College of Medicine, Ilsan-Dong 162, Wonju, Kangwon-Do, Seoul, Korea.
Park
Byong-Gon
BG
Park
Jin-Yong
JY
Lee
Joong-Woo
JW
Lee
Jung-Ha
JH
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000235:genetics; D002413:Cations, Divalent / Q000494:pharmacology*; D002460:Cell Line; D003001:Cloning, Molecular; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D006801:Humans; D009474:Neurons / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002413:Cations, Divalent