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 activity is modulated by another protein, phospholamban (PLB). The levels of both proteins differ in some mammals between atrial and ventricular myocardium and this may lead to differences in relaxation, especially under stimulatory conditions. At a concentration of 100 nM, the beta-adrenergic agonist isoprenaline (ISO) accelerates the relaxation of rat papillary muscle more than that of the left atria (16.4 versus 4.0% hastening of time to 50% relaxation, 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 transients were also abbreviated in ventricular compared to atrial myocytes exposed 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 presence of protein kinase A while that into atrial SR vesicles remained unaffected. Western blotting analysis revealed 23% less SERCA2a protein, but 76% more PLB in ventricular compared to atrial tissue. We conclude that the distinct levels of SERCA2a and PLB in ventricular and atrial myocardium are responsible for the differential modulation of the relaxation process arising from beta-adrenergic stimulation in single rat atrial and ventricular myocytes.
Freestone
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Department of Signalling, Babraham Institute, Cambridge, UK.
Ribaric
S
S
Scheuermann
M
M
Mauser
U
U
Paul
M
M
Vetter
R
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000032:analysis; D000252:Calcium-Transporting ATPases / Q000032:analysis; D004558:Electric Stimulation; D006325:Heart Atria / Q000737:chemistry / Q000166:cytology; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D016276:Ventricular Function; D000099211:Phospholamban
D000318:Adrenergic beta-Agonists; D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D011943:Receptors, Adrenergic, beta; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban