Greater glycogen utilization during β1- than β2-adrenergic receptor stimulation in the isolated perfused rat heart

Author:

McConville Patrick,Lakatta Edward G.,Spencer Richard G.

Abstract

Differences in energy metabolism during β1- and β2-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during β1- compared with β2-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved13C- and31P-NMR spectroscopy was used during β1- and β2-AR stimulation at matched peak workload (2.5 times 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 = LVDP × HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during β1- than β2-AR stimulation with G (54% vs. 38% reduction, P = 0.006) and SF (92% vs. 79% reduction, P = 0.04) perfusions. The greater β1-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However, with SF perfusion, the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during β1- than β2-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, despite a slightly weaker overall inotropic response, during β1- than β2-AR stimulation. These findings are consistent with β1-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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