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K 305 23 May 03 03/05/23 1
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Regulation of E-C Coupling
SNS via the adrenergic b1 receptor Gs- AC and PKA and phosphorylation of: DHPR (b subunit) - increasing open probability phospholamban -increasing SERCA2A activity TnI - increasing off loading of Ca from TnC RyR - increasing fractional release 03/05/23
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E-C coupling in mammalian heart
03/05/23
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Regulation of E-C Coupling
SNS via the adrenergic b1 receptor Gs- AC and PKA and phosphorylation of: DHPR (b subunit) - increasing open probability phospholamban -increasing SERCA2A activity TnI - increasing off loading of Ca from TnC RyR - increasing fractional release PNS – ACh via the muscarinic receptor Gi – reduced AC and PKA 03/05/23
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Regulation of E-C Coupling
Hormones (glucagon, thyroxine etc) Drugs (may simulate SNS effects) Ouabain or digitalis Inhibits Na+ K+ ATPase Increases [Na+]I Decreases Ca2+ efflux via NCX Increases SR Ca2+ loading / release Positive inotropic agent 03/05/23
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03/05/23
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Regulation of Cardiac Output
Inotropic agents affect contractility Chronotropic agents affect heart rate Lusitropic agents affect relaxation 03/05/23
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Regulation of Cardiac Output
Heart rate Stroke Volume Contractility Starling Relationship 03/05/23
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