BACKGROUND: CaMKII activation is proarrhythmic in heart failure where myocardium 
is stretched. However, the arrhythmogenic role of CaMKII in stretched ventricle 
has not been well understood.
OBJECTIVE: We tested abnormal impulse inducibility by stretch current in 
myocytes isolated from CaMKIIδ knockout (KO) mouse left ventricle (LV) where 
CaMKII activity is reduced by ≈ 62%.
METHODS AND RESULTS: Action potentials were recorded by whole-cell patch clamp, 
and abnormal impulses were induced in LV myocytes by a simulation of 
stretch-activated channel (SAC) current. SAC activation failed to induce 
abnormal impulses in wild type (WT) myocytes but steadily produced early 
after-depolarizations and automaticity in KO myocytes in which an increase in 
L-type calcium channel (LTCC) current (I(Ca)) and a reduction of sarcoplasmic 
reticulum Ca(2+) leak and action potential duration (APD) were observed. The 
abnormal impulses were not suppressed by CaMKII inhibitor AIP whereas a low 
concentration of nifedipine eliminated abnormal impulses without shortening APD, 
implicating I(Ca) in promoting stretch-induced abnormal impulses. In addition, 
APD prolongation by LTCC opener S(-)Bay K 8644 or isoproterenol facilitated 
abnormal impulse induction in WT ventricular myocytes even in the presence of 
CaMKII inhibitor AIP, whereas APD prolongation by K(+) channel blocker 
4-aminopyridine promoted abnormal impulses in KO myocytes but not in WT 
myocytes.
CONCLUSION: I(Ca) activation plays a central role in stretch-induced abnormal 
impulses and APD prolongation is arrhythmogenic only when I(Ca) is highly 
activated. At increased I(Ca) activation, CaMKII inhibition cannot suppress 
abnormal impulse induction.