Journal article
Constitutive CaMKII activity regulates Na+ channel in rat ventricular myocytes
Journal of molecular and cellular cardiology, Vol.47(4), pp.475-484
10/01/2009
DOI: 10.1016/j.yjmcc.2009.06.020
PMID: 19591836
Abstract
The cardiac voltage-gated Na+ channel controls the upstroke of action potential and membrane excitability. The Na+ channel associates with Ca2+/CaM-dependent protein kinase (CaMKII), but the role of CaMKII on Na+ channel activity in the resting state is not clear. In this report, we investigated whether CaMKII constitutively regulates Na+ currents (I-Na), independent of Ca2+ influx in rat ventricular myocytes using patch clamp technique. CaMKII inhibition (by KN93 or autocamtide-related inhibitory peptide) caused a negative shift in I-Na steady-state inactivation and delayed recovery from slow inactivation, limiting channel availability. The reduction of I-Na was 29.47 +/- 3.01% at a holding potential (V-h) of -120 mV and it increased to 77.70 +/- 7.92% when V-h was -70 mV, suggesting that near the resting membrane potential, three-quarters of I-Na depends on CaMKII action. CaMKII inhibition also enhanced intermediate inactivation, as well as delayed recovery from fast inactivation, and decreased late I-Na. KN92, an inactive analog of KN93, had no effect on I-Na. Using an antibody against phosphorylated (activated) CaMKII, we found that constitutively active CaMKII coimmuno-precipitated with Na+ channels under resting conditions. CaMKII inhibitors reduced the level of phosphorylated CaMKII, which correlated with the degree of reduction in channel availability. These data suggest that CaMKII in an active form contributes to regulating I-Na. Finally, we observed a drastic reduction in the upstroke velocity of action potentials upon CaMKII inhibition. In conclusion, CaMKII constitutively regulates cardiac Na+ channel and this regulatory mechanism is important for the maintenance of Na+ channel characteristics under physiological conditions. (C) 2009 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Constitutive CaMKII activity regulates Na+ channel in rat ventricular myocytes
- Creators
- Jin-Young Yoon - Sungkyunkwan UniversityWon-Kyung Ho - Seoul National University HospitalSeong-Tae Kim - Sungkyunkwan UniversityHana Cho - Sungkyunkwan University
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.47(4), pp.475-484
- Publisher
- Elsevier
- DOI
- 10.1016/j.yjmcc.2009.06.020
- PMID
- 19591836
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Number of pages
- 10
- Grant note
- A080604 / ministry for health, welfare and family affairs, Republic of Korea; Ministry of Health & Welfare (MOHW), Republic of Korea Korean Ministry of Education; Ministry of Education (MOE), Republic of Korea
- Language
- English
- Date published
- 10/01/2009
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359592202771
Metrics
7 Record Views