Cardiac Physiology: Action Potentials

Action Potentials 

• Different parts of the heart have characteristic action potentials.
• Two main types of action potentials can be seen:
  • Those in Automatic Cells (such as the SA node)
  • Those in Non-Automatic Cells (such as ventricular muscle)

Action potential in Non-Automatic Cells (ex. Ventricular cells)

• The action potential at the SA node (automatic cells), is characterized by a phase IV diastolic depolarization (aka a slow drift in the membrane potential towards threshold).
• Non-Automatic cells have a constant membrane potential until they are depolarized to threshold by a signal started at the pacemaker.
  • What normally maintains membrane potential?
    • Selective Permeability to ions such as Na+, K+, and Ca++
    • Ion gradients
      • Remember that Na+ and Ca++ are prominent extracellularly and K+ is prominent intracellularly.
      • Maintenance of appropriate [K+] is critical for cardiac function.  Ex. Arrhythmias are commonly seen as side effects of diuretics because of associated hypokalemia. Another ex. K+ salts are the components of lethal injections as they build up in the myocytes and slowly cause depolarization and inactivation of Na+ channels.
        • K+ plays such a major role because the membrane is most permeable to K+
      • Ca++ also needs to be tightly regulated. Positive inotropic drugs have a low Safety Index as increased intracellular calcium levels will affect systole and ventricular contraction and cause abnormalities.
    • Membrane proteins that pump ions
      • Na-K ATPase (ATP is dependent on oxygen; Thus gradients in the heart are very sensitive to hypoxia)
      • Na-Ca exchanger (keeps intracellular Ca++ low, brings in Na+)
      • Ca-ATPase (extrudes calcium from cell)

2. Automatic impulse from SA node causes depolarization to threshold (TP on diagram)

3. There is a rapid upstroke (phase 0) due to opening of Na+ channels and influx of Na+ into the cell.

4. Na+ channels eventually inactivate (phase I) but have activated calcium channels to open (phase II). The resulting influx of calcium is responsible for contraction of the cardiac myocyte. Note that phase II (calcium influx) matches up with the ST segment (systole) of the EKG.

5. There is a delayed opening of K+ channels, letting K+ out of the cell, repolarizing the membrane (phase 3).  

• How does the Na+ channel work, again?
  
    
   
  • @ resting membrane potential (- 80 mV), the h-gate (inactivation gate) is open and the m-gate is closed
  • When the membrane is depolarized to threshold (approx -55 mV), the m-gate opens and there is influx of Na+ (phase 0 upstoke). The h-gate then closes, inactivating the channel (phase 1).
    • Scorpion toxins can inactivate the h-gate, severely screwing with membrane potential.
• What about the refractory periods?
  • In the following diagram, dV/dt = responsiveness or membrane to depolarization, available means H-gate is open, M gate is closed, and unavailable means M-gate is open, H-gate is closed.
  • Local anesthetics inactivate sodium channels irregardless of membrane potential.

  
   

  • The ERP (effective refractory period) is when the H-gate is closed and the Na+ channel is in the inactive state (unavailable). Thus, even if further stimuli are sent down from the pacemaker, the myocyte will not depolarize.
    • Antiarrhythmia drugs prolong the ERP to control arrhythmias
    • Conditions like hyperkalemia (secondary to MI, trauma, or certain diuretic use) will depolarize the membrane to a potential similar to the ERP. Notice that many of the Na+ channels will be inactive and the heart will not be very response to electrical signals.
  • The RRP (relative refractory period) is when some H-gates are starting to open up again, allowing for depolarization to occur if the stimulus is there. Notice that stage maps up with the T-wave on the EKG. This is when, due to heterogeneity (some cells can depolarize, others cannot) the heart is vulnerable to an ectopic beat and may experience arrhythmias.
  • The SNP (super normal period) is when due to the open K+ channels, the membrane potential is slightly hyperpolarized. By this point, most of the Na+ channels are back in activated state, and the membrane (if depolarized) will be the most responsive. Keep in mind that during the SNP, the membrane potential is lower than normal, so it will take more of a depolarization to get to threshold, but once threshold is achieved, the upstroke will be more rapid bc more Na+ channels are active).
• It’s about time for a clinical bottom line
  • Extracellular K+ concentration is very important to electrical responsiveness of the heart
  • MI influences the ion gradients and membrane potentials, and electrical responsiveness of the heart
  • Cardiac glycoside toxicity, involving inhibition of the Na+/K+ ATPase, changes the electrical properties of the heart.
     

Automatic Cells have action potentials too, unfortunately

• phase IV diastolic depolarization (aka a slow drift in the membrane potential towards threshold).
  • It is caused by an increase in Ca and Na permeability, and a decrease in K permeability. All this leads to positive charge being sequestered into the cell, leading to depolarization.
  • Sympathetic stimulation at B1 receptors at the sinoatrial node is going to phosphorylate Ca++ channels leading to an increase in Ca++ permeability. Increased intracellular calcium (more positive charge inside the cell) will result in a faster diastolic depolarization phase (as seen in the graph on the left)
  • Parasympathetic stimulation will act on muscarinic receptors on the SA node. Via a G-protein mechanism, K+ conductance increases, resulting in slower diastolic depolarization (the graph on the right) and slower heart rate.
    • Ach leads to atrial arrhytmias.
      • Why? Because atrial muscle cells also have muscarinic receptors. Increased K+ conductance in atrial muscle cells leads to hyperpolarization, resulting in more Na+ channels being activated and the atrial cell becomes more responsive, leading to arrhythmias. (see the table)

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