7 Feb 05 Part II1 PHARMACOLOGY 545 Cardiovascular Pharmacology Cardiac SL ion transport systems Part II 7 February 2005.

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Presentation transcript:

7 Feb 05 Part II1 PHARMACOLOGY 545 Cardiovascular Pharmacology Cardiac SL ion transport systems Part II 7 February 2005

7 Feb 05 Part II2

3

4 Outline Physiological functions of cardiac SL Excitation-contraction coupling Regulation of pH i Metabolism Regulatory receptors Structure of cardiac sarcolemma Excitation-contraction coupling Regulation of pH i

7 Feb 05 Part II5 Na + -Ca 2+ exchanger (NCX)

7 Feb 05 Part II6 NCX 3Na + Ca 2+ E NCX = 3E Na -2E Ca

7 Feb 05 Part II7 E-C coupling in mammalian heart

7 Feb 05 Part II8

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7 Feb 05 Part II11

7 Feb 05 Part II12 transcribe cDNA into cRNA in vitrotranscribe cDNA into cRNA in vitro inject cRNA into Xenopus oocytesinject cRNA into Xenopus oocytes measuring NCX activity cRN A NCX

7 Feb 05 Part II13 NCX Ca 2+ (8 mM) Na (100 mM) extracellular side cytoplasmic side excised giant patch clamp 1  M

7 Feb 05 Part II14

7 Feb 05 Part II15 Ca 2+ dependence of NCX

7 Feb 05 Part II16

7 Feb 05 Part II17

7 Feb 05 Part II18

7 Feb 05 Part II19

7 Feb 05 Part II20 NCX 3Na + Ca 2+ E NCX = 3E Na -2E Ca

7 Feb 05 Part II21 E-C coupling in mammalian heart

7 Feb 05 Part II22

7 Feb 05 Part II23

7 Feb 05 Part II24

7 Feb 05 Part II25

7 Feb 05 Part II26 Store-operated channels (SOC)

7 Feb 05 Part II27

7 Feb 05 Part II28

7 Feb 05 Part II29

7 Feb 05 Part II30