Cardiac CaMKIId splice variants exhibit target signalling specificity and confer sex-selective arrhythmogenic actions in the ischemic-reperfused heart

BELL JR; RAAIJMAKERS AJA; CURL CL; REICHELT ME; HARDING TW; BEI A; NG DCH; ERICKSON JR; VILA PETROFF M; HARRAP SB; DELBRIDGE LMD

INTERNATIONAL JOURNAL OF CARDIOLOGY

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2014 p. 288 - 296

0167-5273

Abstract BACKGROUND: Ischemia-related arrhythmic incidence is generally lower in females (vs males), though risk is selectively increased in women with underlying cardiopathology. Ca2+/calmodulin dependent kinase II (CaMKII) has been implicated in ischemia/reperfusion arrhythmias, yet the role of CaMKII in the ischemic female heart has not been determined. The aim of this study was to define the role and molecular mechanism of CaMKII activation in reperfusion arrhythmias in male/female hearts. METHODS AND RESULTS: Male and female rat hearts and cardiomyocytes were subjected to multiple arrhythmogenic challenges. An increased capacity to upregulate autophosphorylated CaMKII (P-CaMKII) in Ca2+-challenged female hearts was associated with an enhanced ability to maintain diastolic function. In ischemia/reperfusion, female hearts (vs male) exhibited less arrhythmias (59±18 vs 548±9, s, p