Distinct roles of CaM and Ca<SUP>2+</SUP>/CaM-dependent protein kinase II in Ca<SUP>2+</SUP>-dependent facilitation and inactivation of cardiac L-type Ca<SUP>2+</SUP> channels

• Nie Hong-Guang

  Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan School of Pharmaceutical Sciences, China Medical University, Shenyang, China

• Hao Li-Ying

  Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan School of Pharmaceutical Sciences, China Medical University, Shenyang, China

• Xu Jian-Jun

  Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan

• Minobe Etsuko

  Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan

• Kameyama Asako

  Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan

• Kameyama Masaki

  Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan

Bibliographic Information

Other Title

• 心筋L型Ca<SUP>2+</SUP> チャネルのCa<SUP>2+</SUP> 依存性促進および不活性化におけるカルモジュリンおよびCa<SUP>2+</SUP>/カルモジュリン依存性キナーゼIIの異なる役割

Abstract

L-type Ca²⁺ channels have two opposing forms of autoregulatory feedback, Ca²⁺-dependent facilitation (CDF) and Ca²⁺-dependent inactivation (CDI). To explore the underlying mechanisms, we investigated the effects of CaM and CaMKII inhibitors on CDF and CDI with patch clamp technique in guinea-pig ventricular myocytes. We found that both CDF and CDI were depressed and finally abolished by CaM inhibitors, chlorpromazine (1-100 μM) and calmidazolium (1 μM). In contrast, CaMKII inhibitors, KN-62 (0.1-3 μM) and autocamtide 2-related inhibitory peptide (1 μM), delayed the development of CDF and CDI significantly, but did not depress both CDF and CDI. A CaM-binding GST-fusion peptide containing a. a. 1509-1791 of the C-terminal region of guinea-pig Cav1.2 (CT1) is prepared. In pull-down assay, CT1 treated with CaMKII shows a higher affinity for CaM than that treated with phosphatase. Conclusion: Both CaMKII phosphorylation and binding of CaM to the channel are involved in the process of CDF and CDI. We propose a hypothesis that CaM is a key molecule to bifurcate Ca²⁺ signal to CDF and CDI, while CaMKII plays a modulatory role. Acknowledgements: This work was supported by the grants from the Japan Society for the Promotion of Science and the National Natural Science Foundation of China (No.30670761). [J Physiol Sci. 2008;58 Suppl:S46]

Journal

• Proceedings of Annual Meeting of the Physiological Society of Japan

  Proceedings of Annual Meeting of the Physiological Society of Japan 2008 (0), 046-046, 2008

  PHYSIOLOGICAL SOCIETY OF JAPAN

Keywords

• ion channel
• calmodulin
• CaMKII

Details

• CRID: 1390282680706570752
• NII Article ID: 130007039495
• DOI: 10.14849/psjproc.2008.0.046.1
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed