Dissecting the functional role of different isoforms of the L-type Ca2+ channel

Abstract

There currently exist a great number of different mouse lines in which the activity of a particular gene of interest has been inactivated or enhanced. However, it is also possible to insert specific mutations in a gene so that the pharmacological sensitivity of the gene product is altered. An example of such an approach shows how the abolition of the sensitivity of an L-type Ca(2+) channel isoform to dihydropyridines allows the investigation of the physiological role of these channels in different tissues.

Figure 1

LTCCs are multimeric complexes of subunits formed by an α1 pore-forming protein associated to three auxiliary subunits (α2-δ, β, and γ). Four genes encode the pore-forming subunit (Ca_v1.1_Ca_v1.4). The primary structure, α1, is represented in the figure showing the four domains composed of six transmembrane segments. Schematic representation of the knock-in mutation in the Ca_V1.2 gene (Thr1066 to Tyr) realized by Sinnegger-Brauns and coworkers in this issue of the JCI (2) to discriminate in vivo the contributions of Ca_V1.2 and Ca_V1.3 to various physiological functions.