Adenosine A(2a)-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms

Adenosine A(2a) receptor (A(2a)R) stimulation enhances the shortening of ve ntricular myocytes. Whether the A(2a)R-mediated increase in myocyte contrac tility is associated with alterations in the amplitude of intracellular Ca2 + transients was investigated in isolated, contracting rat ventricular myoc ytes using the Ca2+-sensitive fluorescent dye fura 2-AM. In the presence of intact inhibitory G protein pathways, 10(-4) M 2-p-(2-carboxyethyl)pheneth yl-amino-5'-N-ethylcarboxamido-adenosine (CGS-21680), an A(2a)R agonist, in significantly increased Ca2+ transients by 8 +/- 5%, whereas myocyte shorte ning increased by 54 +/- 1%. In contrast, 2 x 10(-7) M isoproterenol, a bet a-adrenergic receptor agonist, increased Ca2+ transients by 104 +/- 15% and increased myocyte shortening by 61 +/- 6%. When A(2a)R were stimulated in myocytes that had the antiadrenergic actions of adenosine (Ado) abolished b y either treatment with pertussis toxin (PTx) or the presence of 8-cyclopen tyl-1,3-dipropylxanthine (DPCPX), an adenosine A(1)-receptor antagonist, th e maximum increases in Ca2+ transients were similarly nominal (with PTx: 10 (-4) M CGS-21680, 14 +/- 6% and 10(-4) M Ado, 15 +/- 4%; without PTx: 10(-5 ) M Ado + 2 x 10(-7) M DPCPX, 19 +/- 1%). These results indicate that compa red with P-adrenergic stimulation, which markedly increases myocyte Ca2+ tr ansients and shortening, A(2a)R-mediated increases in myocyte shortening ar e accompanied by only modest increases in Ca2+ transients. These observatio ns suggest that the A(2a)R-induced contractile effects are mediated predomi nantly by Ca2+-independent inotropic mechanisms.