QUESTIONS

1. Describe the different phases of the action potential in both the myocardial cell and in the conduction fiber or pacemaker cell.
    
2. Is skeletal muscle affected by calcium channel blockers?
   
3. What effect do calcium channel blockers have on vascular smooth muscle?
    
4. Calcium channel blockers are:  (choose positive or negative)
   
        positive/negative inotropes
        positive/negative lusitropes
        positive/negative dromotropes
    
5. Knowing the above info, what might be the main indications for & then adverse effects of calcium channel blockers.
   
   
   
   
    

ANSWERS

1. Here goes:
   
   PHASE ZERO:  OK, we're hanging out w/a resting potential of -90mV if we're a myocardial cell & -60mV if we're a conduction cell.  This number reflects the charge difference between the inside of the cell relative to the outside of the cell.  Because it is more positive outside the cell, there is a "negative" sign involved.
   
   So phase zero starts.  The sodium gates (affectionately known as "fast sodium channels") open & Na+ goes running inside.  (Remember, it is more negative inside & those positive sodiums are attracted). A steep depolarization results actually taking the action potential into the positive range.
   
   That's if you're the myocardial cell.  If you're a conduction cell, you don't have fast sodium channels :( Instead, you have slow calcium channels. Calcium runs in instead of sodium.  Ok, it doesn't run in, it kind of moseys in.  The depolarization phase of the conduction cell is much less steep.
   
   PHASE ONE:  The K+ gates open & K+ runs out.  There's so much positive coming in, the K+ is repelled & runs out as soon as it has the opportunity to do so.  So depolarization stops & repolarization starts.  I believe this is the same in both conduction & myocardial cells.
   
   PHASE TWO:  There is no phase two in the conduction cell.  In phase two, the slow calcium channels open (in the conduction cell they are already open).  Calcium comes into the cell gradually. This creates a plateau in the action potential of the myocardial cell as K+ going out is balanced by Ca++ coming in.  Note that all the calcium coming in is noted by the sarcoplasmic reticulum which says, " Wow, the calciums are arriving from the outside!  It must be time for the calcium party!"  Not wanting its own sequestered calciums to be left out of the calcium party, the sarcoplasmic reticulum releases its own calcium.  Now the myocardial cell has a TON of calcium to bind to troponin & participate in muscle contraction. (The calcium channels of the sarcoplasmic reticulum open in response to the presence of other calcium in the cytoplasm.)
   
   PHASE THREE:  The calcium channels close & K+ continues running out.  Repolarization becomes steep again.  (Occurs in both the myocardial cell & in the conduction cell.)
   
   PHASE FOUR:  The K+ gates close.  And what a mess!  We have K+ on the outside of the cell & Na+ on the inside.  The Na+/K+ pumps get going to set things right.
   
   (Er, Paul?  How do we get back up to threshold to start the whole thing over again?)
   
   
   
   
    
2. Nope.  Skeletal muscle doesn't need extracellular calcium for muscle contraction.  It just uses it's sarcoplasmic reticulum.  (And I guess the calcium channels on the sarcoplasmic reticulum don't get affected by calcium channel blockers because the drug doesn't get intracellular?)
   
   
   
   
    
3. They dilate arterioles in the systemic circulation. Veins & pulmonary vascular doesn't seem to respond.  This leads to a drop in peripheral resistance & thus a drop in blood pressure.  This may be enough to stimulate baroreceptors & give an initial increase in blood pressure first depending on which calcium channel blocker you are using. 
   
   The original "big three" calcium channel blockers in vet med are: nifedipine, verapamil, & diltiazem.  They have been joined by amlodipine which is most closely related to nifedipine. 
   
   In terms of treating hypotension, nifedipine & amlodipine seem to be the main drugs that affect arteriolar smooth muscle.
   
   
   
   
    
4. Calcium channel blockers are: negative inotropes, positive lusitropes (meaning they relax heart muscle/make it more compliance), and negative dromotropes (meaning that they slow conduction through the AV node).
   
   
   
   
    
5. Calcium channel blockers block conduction cell phase zero.  This makes the depolarization even less steep, and prolongs the whole action potential.  This is how they slow conduction at the AV node.  (Well, here its really diltiazem & verapamil that are good at this).  They also prolong the refractory period.
   
   
   
   
    
6. In phase two in the myocardial cell, the calcium channel blockers prevent the entrance of normal large amounts of calcium. This means less guests at the calcium party :) and less calcium for muscle contraction.  (Negative inotropic effect).
   
   Basically indications for calcium channel blockers are hypertension, supraventricular arrhythmias, atrial fib, & HCM.  Potential adverse effects are hypotension & AV block.
   
   I feel like I should end this set with "is this right, Paul?"  (I used all of Paul's articles that I could find to write this)