Differential lusitropic responsiveness to beta-adrenergic stimulation in rat atrial and ventricular cardiac myocytes

Cardiac myocyte relaxation is brought about mainly through Ca2+ uptake into the sarcoplasmic reticulum (SR) by a Ca2+-ATPase isoform, SERCA2a. Its act ivity is modulated by another protein, phospholamban (PLB). The levels of b oth proteins differ in some mammals between atrial and ventricular myocardi um and this may lead to differences in relaxation, especially under stimula tory conditions. At a concentration of 100 nM, the P-adrenergic agonist iso prenaline (ISO) accelerates the relaxation of rat papillary muscle more tha n that of the left atria (16.4 versus 4.0% hastening of time to 50% relaxat ion, respectively). Ventricular myocytes were 24.7% quicker in reaching 50% of their diastolic length after contraction when treated with ISO compared to atrial myocytes, which were only 3.6% faster. Ca2+ fluorescence transie nts were also abbreviated in ventricular compared to atrial myocytes expose d to ISO (41.9 versus 25.2% hastening of time to 50% peak Ca2+ respectively ). Ca2+ uptake into ventricular SR vesicles was increased by 13% in the pre sence of protein kinase A while that into atrial SR vesicles remained unaff ected. Western blotting analysis revealed 23% less SERCA2a protein, but 76% more PLB in ventricular compared to atrial tissue. We conclude that the di stinct levels of SERCA2a and PLB in ventricular and atrial myocardium are r esponsible for the differential modulation of the relaxation process arisin g from P-adrenergic stimulation in single rat atrial and ventricular myocyt es.