Constitutive β₂‐adrenergic signalling enhances sarcoplasmic reticulum Ca²⁺ cycling to augment contraction in mouse heart

Abstract

Excitation-Ca¥ release coupling is a pivotal event in cardiac function. During membrane depolarization, sarcolemmal Ca¥ influx through the voltage-operated L_type Ca¥ channels triggers the sarcoplasmic reticulum (SR) to release Ca¥ via the Ca¥-induced Ca¥ release (CICR) mechanism (Fabiato, 1983). The resultant cytosolic Ca¥ transient activates myofilament proteins and initiates contraction. Cardiac relaxation ensues when the elevated cytoplasmic Ca¥ is resequestered by the SR Ca¥ pump, or, to a lesser extent, extruded via the sarcolemmal Na¤-Ca¥ exchanger. In order to meet the body's variable circulatory demands, cardiac excitation-contraction (EC) coupling is constantly modulated by an array of physiological mechanisms. Driven by sympathetic neurotransmitters and adrenal hormones, â_adrenergic receptor (âAR) signalling interacts with virtually all constituents of the EC coupling cascade, including the L_type Ca¥ channel current (ICa) (Tsien et al. 1986;Xiao & Lakatta, 1993), SR Ca¥ release channels/ ryanodine receptors (RyRs) (Yoshida et al. 1992;, phospholamban (PLB) (Lindemann et al. 1983;Kuschel et al. 1999a), and contractile myofilaments (Rapundalo et al. 1989; Kuschel et al. 1999b). Additionally, â_adrenergic stimulation may modulate other sarcolemmal ionic currents, such as K¤ currents (Scamps, 1996), and electrogenic transporters, such as Na¤-Ca¥ exchanger (in non-mammalian species) (Shuba et al. 1998), to alter the

FKBP12.6 overexpression decreases Ca2+ spark amplitude but enhances [Ca2+]i transient in rat cardiac myocytes

“…The distributions of these characteristics were asymmetrical due to detection limits of the smaller Ca 2ϩ sparks. Broad modal distribution of Ca 2ϩ spark amplitudes has been described earlier (8,12,17,29,35) and differs from the monotonic decaying distribution theoretically predicted (5), probably because the present method restricted the "out-of-focus" events. Ca 2ϩ spark distribution has been previously adjusted to a simple (20), bimodal (31), or multicomponent (30) Gauss function.…”

Rodent models of heart failure: an updated review

“…Despite this concern, transactivator lines have been developed that show no cardiotoxicity for at least 6 months, and so these experimental limitations can be easily circumvented [250]. cycling of the SR, which showed decreased PLN expression [242,326] Other studies showed that mice die earlier from severe HF indicated by cardiac dilation, pulmonary congestion and pleural effusion [58,159] In CHF, there is selective down-regulation of b1-AR and desensitization of both b1-AR and b2-AR (mediated by b-ARK1)…”

Adenovirus Vector E4 Gene Regulates Connexin 40 and 43 Expression in Endothelial Cells via PKA and PI3K Signal Pathways

“…32 Both of ␤ 1 AR and ␤ 2 AR stimulate the classic G s -adenylyl cyclase-3Ј,5Ј-adenosine monophosphate (cAMP) protein kinase A (PKA) signaling cascade. 33 Therefore, activation of ␤-adrenergic receptors may also involve a cAMP-independent mechanism in the regulation of Cx expression.…”