Histidine residues in the IS3-IS4 loop are critical for nickel-sensitive inhibition of the Ca sub(v)2.3 calcium channel

• Published in: FEBS letters Vol. 581; no. 30; pp. 5774 - 5780
• Main Authors: Kang, H W, Moon, HJ, Joo, Sh, Lee, J H
• Format: Journal Article
• Language: English
• Published: 22.12.2007
• ISSN: 0014-5793
• DOI: 10.1016/j.febslet.2007.11.045

We recently reported that a histidine (H191) in the S3-S4 loop of domain I is critical for nickel inhibition of the Ca sub(v)3.2 T-type Ca super(2) super(+) channel. As in Ca sub(v)3.2, two histidine residues are commonly found in the IS3-IS4 loops of mammalian Ca sub(v)2.3 Ca super(2) super(+) channels, which are also blocked by low micromolar concentrations of nickel. We show here by site-directed mutagenesis and electrophysiology that both residues contribute to the nickel sensitivity of Ca sub(v)2.3, with H183 being more critical than H179. These findings strongly suggest that both H179 and H183 in the IS3-IS4 loop are essential structural determinants required for nickel sensitive inhibition of the Ca sub(v)2.3.