18.3 excitability in the myocardium (AP in contractile cardiomyocytes)

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0 phase (resting membrane potential)

  • typically betw. -80mV and -90mV

  • resting membrane more negative due to protective/more intentional than skeletal muscle (no twitches)

  • created from continuous EFFLUX (moving out) of K+ through inward rectifier potassium channels (KIR) (keeps membrane potential low)

  • small amount of Ca+2 and Na+ permeability

  • Na/K/ATPase serves to maintain concentration gradients

<ul><li><p>typically betw. <mark data-color="yellow" style="background-color: yellow; color: inherit">-80mV and -90mV</mark></p></li><li><p>resting membrane <strong><u>more negative</u></strong> due to protective/more intentional than skeletal muscle (<strong><u>no twitches</u></strong>)</p></li><li><p>created from <strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>continuous EFFLUX (moving out) of K<sup>+</sup> through </u></mark></strong><span style="color: red"><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>inward rectifier potassium channels (K<sub>IR</sub>) </u></mark></strong></span><span style="color: #ffffff"><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>(keeps membrane potential low)</u></mark></strong></span></p></li><li><p><span style="color: #ffffff">small amount of Ca<sup>+2</sup> and Na<sup>+</sup> permeability</span></p></li><li><p><span style="color: #ffffff"><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>Na/K/ATPase serves to maintain concentration gradients</u></mark></strong></span></p></li></ul><p></p>
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  1. depolarization

  • similar process in skeletal muscle

  • voltage-gated fast sodium channels (Naf) are activated, allowing influx of positively charged sodium ions

  • cells are becoming more positive (depolarization)

<ul><li><p>similar process in skeletal muscle</p></li><li><p><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>voltage-gated </u></mark><span style="color: red"><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>fast sodium channels (Na<sub>f</sub>)</u></mark></strong></span><span style="color: #ffffff"><mark data-color="yellow" style="background-color: yellow; color: inherit"> are activated, allowing </mark><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>influx</u></mark></strong><mark data-color="yellow" style="background-color: yellow; color: inherit"> of </mark><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>positively charged sodium ions</u></mark></strong></span></p></li><li><p><span style="color: #ffffff">cells are becoming more <strong><u>positive (depolarization)</u></strong></span></p></li></ul><p></p>
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  1. transient repolarization

  • voltage-gated sodium channels rapidly inactivate at the peak of AP

  • sodium permeability decreases since it’s TOO positive

  • cardiomyocytes go into refractory period

    • membrane potential begins to hyperpolarize due to transient outward current from K channels (K channels help maintain refractory)

<ul><li><p>voltage-gated sodium channels rapidly inactivate at the <strong><u>peak</u></strong> of AP</p></li><li><p>sodium permeability <mark data-color="yellow" style="background-color: yellow; color: inherit"><u>decreases since it’s TOO positive</u></mark></p></li><li><p>cardiomyocytes go into <strong><u>refractory period</u></strong></p><ul><li><p><mark data-color="yellow" style="background-color: yellow; color: inherit">membrane potential begins to </mark><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>hyperpolarize</u></mark></strong><mark data-color="yellow" style="background-color: yellow; color: inherit"> due to transient outward current from K channels (K channels help maintain refractory)</mark></p></li></ul></li></ul><p></p>
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  1. plateau phase

  • voltage-gated L-type calcium channels (CaL) OPEN, bringing postively-charged Ca2+ ions into cell

  • this is opposed by the efflux of K+ ions through delayed rectifier potassium channels (KDR)

  • two opposite electrical forces create plateau in membrane potential

<ul><li><p>voltage-gated <span style="color: red"><strong><mark data-color="yellow" style="background-color: yellow; color: inherit"><u>L-type calcium channels (Ca<sub>L</sub>) OPEN</u></mark></strong><mark data-color="yellow" style="background-color: yellow; color: inherit">,</mark></span> bringing postively-charged Ca2+ ions into cell</p></li><li><p>this is <u>opposed</u> by the efflux of K+ ions through <strong><u>delayed rectifier potassium channels (K<sub>DR</sub>)</u></strong></p></li><li><p>two opposite electrical forces create plateau in membrane potential</p></li></ul><p></p>
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  1. rapid repolarization

  • L-type calcium channels close

  • efflux of K+ continues through voltage gated potassium channels

  • membrane potential repolarizes to resting state

<ul><li><p>L-type calcium channels close</p></li><li><p><strong><u>efflux of K+ continues through voltage gated potassium channels</u></strong></p></li><li><p>membrane potential repolarizes to resting state</p></li></ul><p></p>
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excitation contraction coupling

couples together the excitation of cardio myocytes with the contraction (AP traveling thru the muscle)

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calcium induced calcium released (CICR)

the Ca+ goes through the LTCC (L-type calcium channel, voltage gated), is enough to open the “door” (Rynodine receptor, RyR) and is enough to induce Ca+ release from the sarcoplasmic reticulum, but NOT ENOUGH TO STIMULATE A CONTRACTION