Figure 1
Cacna1b exon targeting strategy, and sites of action of three analgesics on Ca V 2.2 channels. A, Illustrates the mouse Cacna1b gene on chromosome 2 between exons 34 and 41. Constitutive exons (gray bars), mutually exclusive exons (red and blue bars) and introns (horizontal line) are shown. The region in Cacna1b targeted by homologous recombination is delineated by two arrows. The targeting construct contains a second copy of e37b to replace wild-type e37a as previously reported [26]. The replacement e37b (dark blue) contains a silent mutation that introduces a unique Xho I site to allow genotyping and tracking of the substituted exon. The possible mRNAs generated from wild-type and e37b-only mice are shown. B, illustrates the sites of actions of gabapentin (CaVα2δ-1), ziconotide (CaV2.2 α1-subunit) and morphine (μ-opioid receptor). Morphine action on CaV2.2-e37a and CaV2.2-e37b channels is different. CaV2.2-e37a channels are inhibited by both voltage-dependent, Gβγ-dependent and voltage-independent, Gβγ-independent pathways, whereas CaV2.2-e37b channels are mostly sensitive to voltage-dependent, Gβγ-dependent inhibition.