Effect of Training Induces Changes in Heart, CaMKII Dependent or Not?

Abstract

Background. Soluble guanylate cyclase (sGC) plays multiple, conflicting roles during sepsis (Am.J. Physiol.,2009;297:H654-663). Here we studied the impact of sGC deficiency on cardiac calcium (Ca 2þ ) handling in sepsis-induced cardiomyopathy (SIC). Methods and Results. Cardiomyocyes were isolated from mice deficient in the a 1 subunit of sGC (sGCa 1 -/-) and wild-type (WT), at baseline and 12h after administration of lipopolysacharide (LPS, 25 mg/g, ip). In sGCa 1 -/cells (vs. WT), LPS induced a more marked decrease in externally paced Ca 2þ transients (DCa i , fura-2AM, Table ), sarcoplasmic reticulum Ca 2þ load (Ca SR , using caffeine applications), fractional release (FR, DCa i / Ca SR ) and trans-sarcolemmal Ca 2þ entry (Ca E , from the first DCa i after caffeine removal). Ca 2þ transient decay (t Ca ) was slower in sGCa 1 -/vs. WT after LPS, while Ca 2þ decay during caffeine (t Caff , measuring Na þ /Ca 2þ exchange) and L-type Ca 2þ currents (I Ca,L ) were similar (Table ; for all, n> 25 cells from >4 mice). Conclusions. LPS induces a decrease in I Ca ,L , Ca E , FR, Ca SR and DCa i that does not require sGCa 1 . Moreover, sGC partially protects against Ca 2þ handling alteration in SIC, through yet unidentified mechanisms.