7 Feb 05 Part II 1

PHARMACOLOGY 545

Cardiovascular Pharmacology

Cardiac SL ion transport systemsPart II

7 February 2005

7 Feb 05 Part II 2

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7 Feb 05 Part II 4

OutlinePhysiological functions of cardiac SL

Excitation-contraction coupling

Regulation of pHi

Metabolism

Regulatory receptors

Structure of cardiac sarcolemma

Excitation-contraction coupling

Regulation of pHi

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Na+-Ca2+ exchanger

(NCX)

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NCXNCX

3Na3Na++

CaCa2+2+

ENCX= 3ENa-2ECa

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E-C coupling in mammalian heart

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• transcribe cDNA into cRNA in vitrotranscribe cDNA into cRNA in vitro

• inject cRNA into inject cRNA into XenopusXenopus oocytes oocytes

measuring NCX activity

cRNAcRNAcRNAcRNA

NCX

NCX

NCX

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NCX

Ca2+

(8 mM)

Na

(100 mM)

extracellular side

cytoplasmic side

excised giant patch clamp

1 M

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Ca2+ dependence of NCX

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NCXNCX

3Na3Na++

CaCa2+2+

ENCX= 3ENa-2ECa

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E-C coupling in mammalian heart

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-30 mV

+50 mV

-80 mV

1 µm

1 second

10 cpm

25 pA

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Store-operated channels(SOC)

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1st 3rd CAF CON CAF NIF+KB-R CAF

1.0 F/F0

2nd

50 pA

20 S

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0

0.5

1

1.5

2

2.5

CON KB-R 30 LOE 2-APB SK&F-96365

ZnCl2

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0

10

20

30

40

3d 10d 56d

load

SR (

amol

/pF

)1min

10s

7 Feb 05 Part II 30