Submitted on May 9, 2007
Accepted on September 28, 2007
Greater Glycogen Utilization During 
1- than 2-AR Stimulation in the Isolated Perfused Rat Heart
Patrick McConville1, Edward G Lakatta2, and Richard G Spencer3*
1 Magnetic Resonance Imaging and Spectroscopy Section, Laboratory for Clinical Investigation, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States; Laboratory for Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States
2 Laboratory for Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States
3 Magnetic Resonance Imaging and Spectroscopy Section, Laboratory for Clinical Investigation, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: spencerri{at}grc.nia.nih.gov.
Differences in energy metabolism during 
1- and 2- AR stimulation have been shown to translate to differences in the elicited functional responses. Previous findings have suggested that differential access to glycogen during 1-, compared with 2- AR stimulation may influence the peak functional response, and modulation of the response during sustained adrenergic stimulation. Interleaved 13C and 31P NMR spectroscopy was used during (i) 1- and (ii) 2- AR stimulation at matched peak workload (2.5x baseline) in the isolated perfused rat heart to monitor glycogen levels, phosphorylation potential, and intracellular pH. Simultaneous measurements of left ventricular (LV) function (LV developed pressure; LVDP), heart rate (HR), and rate-pressure product (RPP = LVDPxHR) were also performed. Perfusion was performed under both substrate-free (SF) conditions and with exogenous glucose (G) included in the perfusate. Greater glycogenolysis was observed during 1 than during 2- AR stimulation for both G (1:54% reduction; 2:38% reduction; p=0.006 for 1 vs 2) and SF (1:92% reduction; 2:79% reduction; p=0.04 for 1 vs 2) perfusions. The greater level of 1-AR-mediated glycogenolysis was correlated with a greater ability to sustain the initial contractile response. However, during SF conditions, this ability was of limited duration; excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during 1-AR stimulation, compared with 2-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, in spite of a lesser overall inotropic response, during 1- than 2- AR stimulation. These findings are consistent with 1-AR-specific PKA-dependent glycogen phosphorylase kinase signalling.
