Calmodulin-Cork Model of Gap Junction Channel Gating—One Molecule, Two Mechanisms

International Journal of Molecular Sciences

Camillo Peracchia¹ 

[1] Department of Pharmacology and Physiology, School of Medicine and Dentistry, University Rochester, Rochester, NY 14642, USA;

关键词: gap junctions;    connexins;    channel gating;    calcium;    calmodulin;    cell communication;   

DOI  :  10.3390/ijms21144938

来源: DOAJ

【 摘 要 】

The Calmodulin-Cork gating model is based on evidence for the direct role of calmodulin (CaM) in channel gating. Indeed, chemical gating of cell-to-cell channels is sensitive to nanomolar cytosolic calcium concentrations [Ca²⁺]_i. Calmodulin inhibitors and inhibition of CaM expression prevent chemical gating. CaMCC, a CaM mutant with higher Ca²⁺-sensitivity greatly increases chemical gating sensitivity (in CaMCC the NH₂-terminal EF-hand pair (res. 9–76) is replaced by the COOH-terminal pair (res. 82–148). Calmodulin colocalizes with connexins. Connexins have high-affinity CaM binding sites. Several connexin mutants paired to wild-type connexins have a high gating sensitivity that is eliminated by inhibition of CaM expression. Repeated transjunctional voltage (Vj) pulses slowly and progressively close a large number of channels by the chemical/slow gate (CaM lobe). At the single-channel level, the chemical/slow gate closes and opens slowly with on-off fluctuations. The model proposes two types of CaM-driven gating: “Ca-CaM-Cork” and “CaM-Cork”. In the first, gating involves Ca²⁺-induced CaM-activation. In the second, gating takes place without [Ca²⁺]_i rise. The Ca-CaM-Cork gating is only reversed by a return of [Ca²⁺]_i to resting values, while the CaM-Cork gating is reversed by Vj positive at the gated side.

【 授权许可】

Unknown