Acetylcholine increases Ca²⁺ influx by activation of CaMKII in mouse oocytes

IP₃-induced Ca²⁺ release is the primary mechanism that is responsible for acetylcholine (ACh)-induced Ca²⁺ oscillation. However, other mechanisms remain to explain intracellular Ca²⁺ elevation. We here report that ACh induces Ca²⁺ influx via T-type Ca²⁺ channel by activation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), and the ACh-induced Ca²⁺ influx facilitates the generation of Ca²⁺ oscillation in the mouse ovulated oocytes (oocytes_MII). ACh increased Ca²⁺ current by 50 ± 21%, and produced Ca²⁺ oscillation. However, the currents and Ca²⁺ peaks were reduced in Ca²⁺-free extracellular medium. ACh failed to activate Ca²⁺ current and to produce Ca²⁺ oscillation in oocytes pretreated with KN-93, a CaMKII inhibitor. KN-92, an inactive analogue of KN93, and PKC modulators could not prevent the effect of ACh. These results show that ACh increases T-type Ca²⁺ current by activation of CaMKII, independent of the PKC pathway, in the mouse oocytes.