Title : A molecular determinant of nickel inhibition in Cav3.2 T-type calcium channels.

Pub. Date : 2006 Feb 24

PMID : 16377633






8 Functional Relationships(s)
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1 From pharmacological analysis of the recombinant T-type channels, low concentrations (<50 microM) of nickel were found to selectively block the Ca(v)3.2 over the other isoforms. Nickel immunoglobulin lambda variable 7-43 Homo sapiens
2 To date, however, the structural element(s) responsible for the nickel block on the Ca(v)3.2 T-type Ca2+ channel remain unknown. Nickel immunoglobulin lambda variable 7-43 Homo sapiens
3 Thus, we constructed chimeric channels between the nickel-sensitive Ca(v)3.2 and the nickel-insensitive Ca(v)3.1 to localize the region interacting with nickel. Nickel immunoglobulin lambda variable 7-43 Homo sapiens
4 Systematic assaying of serial chimeras suggests that the region preceding domain I S4 of Ca(v)3.2 contributes to nickel block. Nickel immunoglobulin lambda variable 7-43 Homo sapiens
5 Point mutations of potential nickel-interacting sites revealed that H191Q in the S3-S4 loop of domain I significantly attenuated the nickel block of Ca(v)3.2, mimicking the nickel-insensitive blocking potency of Ca(v)3.1. Nickel immunoglobulin lambda variable 7-43 Homo sapiens
6 Point mutations of potential nickel-interacting sites revealed that H191Q in the S3-S4 loop of domain I significantly attenuated the nickel block of Ca(v)3.2, mimicking the nickel-insensitive blocking potency of Ca(v)3.1. Nickel immunoglobulin lambda variable 7-43 Homo sapiens
7 Point mutations of potential nickel-interacting sites revealed that H191Q in the S3-S4 loop of domain I significantly attenuated the nickel block of Ca(v)3.2, mimicking the nickel-insensitive blocking potency of Ca(v)3.1. Nickel immunoglobulin lambda variable 7-43 Homo sapiens
8 These findings indicate that His-191 in the S3-S4 loop is a critical residue conferring nickel block to Ca(v)3.2 and reveal a novel role for the S3-S4 loop to control ion permeation through T-type Ca2+ channels. Nickel immunoglobulin lambda variable 7-43 Homo sapiens