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Adenosine A2A and {beta}-adrenergic calcium transient and contractile responses in rat ventricular myocytes | Author(s) | James G. Dobson, Jr., Lynne G. Shea, Richard A. Fenton | | Journal | Am J Physiol Heart Circ Physiol, Oct 2008; 10.1152/ajpheart.00927.2008. | Method Extract | | calcium contractility | Abstract | The adenosine A2A receptor ( A2AR) enhances cardiac contractility and the adenosine A1R receptor (A1R) is antiadrenergic by reducing the adrenergic  1 receptor (1R)-elicited increase in contractility. In this study we compared the A2AR-, A1R- and 1R-elicited actions on isolated rat ventricular myocytes in terms of calcium transient and contractile responses involving protein kinase A (PKA) and protein kinase C (PKC). Stimulation of A2AR with 2 µM (~EC50) CGS-21680 (CGS) produced a 17-28% increase in the Ca transient ratio (CTR) and maximum velocities (Vmax) of transient ratio increase (+MVT) and recovery (-MVT), but no change in the time-to-50% recovery (TTR). CGS increased myocyte sarcomere shortening (MSS) and the Vmax of shortening (+MVS) and relaxation (-MVS) by 31-34% with no change in time-to-50% relengthening (TTL). 1R stimulation using 2 nM (~EC50) isoproterenol (ISO) increased CTR, +MVT, -MVT by 67-162% and decreased TTR by 43%. ISO increased MSS, +MVS, -MVS by 153-174% and decreased TTL 31%. The A2AR and 1R Ca transient and contractile responses were not additive. The PKA inhibitor Rp-cAMPS prevented both the CGS and ISO-elicited contractile responses. The PKC inhibitors chelerythrine and KIE1-1 peptide (PKC specific) prevented the antiadrenergic action of A1R, but did not influence in A2AR-mediated increases in contractile variables. The findings suggest that cardiac A2AR utilize cAMP/PKA like 1R, but the Ca transient and contractile responses are less in magnitude and not equally affected. While PKC is important in the A1R antiadrenergic action, it does not seem to play a role in the A2AR-elicited Ca transient and contractile events. |
| Keywords | hyperswithc, calcium, contractility, sarcomere length | Our Ref: 1702
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