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Figures for Movsesian lectures on inotropy and vasodilatation

Figures for Movsesian lectures on inotropy and vasodilatation. Troponin I Troponin C Troponin T. Tropomyosin. Actin. Low ATPase activity. Myosin. Ca 2+. Troponin I Troponin C-Ca 2+ Troponin T. Tropomyosin. Actin. High ATPase activity and contraction. Myosin.

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Figures for Movsesian lectures on inotropy and vasodilatation

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  1. Figures for Movsesian lectures on inotropy and vasodilatation

  2. Troponin I Troponin C Troponin T Tropomyosin Actin Low ATPase activity Myosin Ca2+ Troponin I Troponin C-Ca2+ Troponin T Tropomyosin Actin High ATPase activity and contraction Myosin Thin filament regulation of contraction in cardiac myocytes

  3. Ca2+ influx and release in cardiac myocytes Ca2+ Na+ Ca2+ Sarcolemma Ca2+ channel (L-type) Na+ channel Na+/Ca2+ exchanger Ca2+ channel (Ry-sensitive) Na+ Ca2+ Sarcoplasmic reticulum

  4. Ca2+ sequestration and efflux in cardiac myocytes Na+ Sarcolemma Na+/Ca2+ exchanger Ca2+ Sarcoplasmic reticulum SERCA2 Ca2+

  5. cAMP-mediated signalling 1: receptor-stimulated cAMP generation  -adrenergic receptor -adrenergic receptor Gb Gb Adenylate cyclase Gg Gg Gas Gas* GDP GTP cAMP (active) Phosphodiesterase AMP (inactive)

  6. cAMP-mediated signalling 2: activation of cAMP-dependent protein kinase and the phosphorylation of protein substrates PK-A (inactive) cAMP Protein PK-A (active) Phosphatase cAMP Protein PO43-

  7. PK-A substrates in cardiac myocytes involved in inotropy Ca2+ Sarcolemma Ca2+ channel (L-type)  Adenylate cyclase -adrenergic receptor P G Ca2+ channel (Ry-sensitive) G ATP P Ca2+ cycling G cAMP PK-A Ca2+ Sarcoplasmic reticulum PL P SERCA2 Ca2+

  8. Drug Relative affinity for receptor Cardiovascular actions  1 cardiac 2 cardiac, vascular  heart rate  contraction vasoconstriction noradrenaline (norepinephrine) ++++ ++    adrenaline (epinephrine) ++++ ++++ +    dopamine ++ ++++ ++    dobutamine ++++ +++    isoproterenol ++++ ++++   

  9. Thick filament regulation of contraction in vascular myocytes Actin Low ATPase activity Myosin Ca2+ Ca2+-Calmodulin- Myosin kinase Actin High ATPase activity and contraction Myosin~PO43_ Phosphatase Phosphatase~PO43- PK-G Myosin

  10. Ca2+ influx, release and efflux in vascular myocytes Ca2+ -adrenergic angiotensin Sarcolemma Ca2+ channel (L-type) Ca2+-ATPase Receptor Gq Ca2+ Phospholipase C Ca2+ channel IP3-sensitive PI IP3 Ca2+ SERCA2 Ca2+ Sarcoplasmic reticulum

  11. Ca2+ influx and release in vascular myocytes and its modulation by PK-G Ca2+ -adrenergic angiotensin Sarcolemma Ca2+ channel (L-type) Receptor Gq Closes Ca2+ channels Phospholipase C Reduces IP3 generation Ca2+ channel IP3-sensitive PI IP3 IRAG Reduces IP3-mediated Ca2+ release Ca2+ Sarcoplasmic reticulum PK-G Activated by cGMP and cAMP

  12. cGMP-mediated signalling in smooth muscle and sites of drug action Natriuretic peptides Guanylate cyclase, membrane-bound Ca2+-calmodulin PDE1 cGMP GTP GMP Guanylate cyclase, soluble PDE5 Sildenafil Nirates Nitroprusside Hydralazine? Activation of PK-G  Ca2+ influx (activation of K+ channels)  intracellular Ca2+ release (IP3 generation, IRAG phosphorylation)  myosin phosphorylation (activation of myosin phosphatase)

  13. cAMP-mediated signalling in smooth muscle and sites of drug action -adrenergic receptor agonists Adenylate cyclase, membrane-bound cAMP ATP AMP PDE3 Milrinone, enoximone, cilostazol Activation of PK-G  Ca2+ influx (activation of K+ channels)  intracellular Ca2+ release (IP3 generation, IRAG phosphorylation)  myosin phosphorylation (activation of myosin phosphatase)

  14. Bradykinin Acetylcholine BK receptor M3 receptor G proteins PI Receptor-operated Ca2+ channel Phospholipase C IP3 DAG Ca2+ influx Ca2+ release [Ca2+] CaM Protein kinase C L-arginine Phospholipids Phospholipase A2 NO synthase Arachidonic acid L-citrulline NO Cyclooxygenase Prostacyclin Nitroprusside Vascular relaxation Endothelium-dependent vasodilatation

  15. Vasoconstriction Angiotensinogen Angiotensin II Angiotensin I Angiotensin-converting enzyme Renin Rubbish Bradykinin Vasodilatation

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