Potassium (Addendum)

Front 1

Hyperkalemia increases pK and hypokalemia decreases pK. Isn't this counter to the flow of ions down its concentration gradient?

Back 1

Permeability is different from concentration gradient. Concentration gradient takes into account the electrical and chemical gradients. Permeability simply refers to the external concentration and its ability to enter the cell. The greater the external concentration, the greater the permeability.

Total flow is determined by two factors: the pressure behind the valve (gradient) and the amount the valve is opened (permeability). These two variables are independent for both the hose and the K+ channels. In the case of the K+ channels, the external K+ concentration determines how much the valve is open (permeability); the Ko/Ki gradient determines the pressure.

The electrical and chemical gradient and the permeability are all factors that determine the actual movement of potassium.

Front 2

Why does high extracellular potassium increase the permeability of pacemaker cells for potassium?

Back 2

K+ acts on Mg2+, which blocks the inward rectifying K+ channel

Net effect on pacemaker cells is to increase resting K+ permeability relative to Na+ leak through pacemaker channels leading to hyperpolarization and a slowing of pacemaker rate. The net effect is different in non-nodal cells, since there is little pacemaker current and an increase in K_ will affect membrane potential mainly through a change in the K+ equilibrium potential

Front 3

Hyperkalemia causes the RMP of cardiac muscle cells to become less negative (more positive) (towards depolarization). Hypokalemia causes the RMP to become more negative (hyperpolarized) explain.

Back 3

RMP is dependent upon the permeability of the cells to ions and the concentration gradient. Thus, in hyperkalemia, the concentration gradient is reduced (usually more concentrated inside cell), resulting in the RMP going away from the K+ membrane potential of -95mV. This may lead to increased excitability. HOWEVER, in severe hyperkalemia, Na+ inactivation gates close. Thus, fewer Na+ gates are available, so the cell is less excitable. Thus, hyperkalemia can make cells more excitable up to a point beyond which it then makes cells less excitable.

Front 4

Explain how hyperkalemia, hypokalemia, or an antiarrhythmic drug can cause arrhythmias.

Back 4

Hyperkalemia:
Non-pacemaker cells --> decreases conduction velocity (because of effect on Na+ inactivation gates) that may lead to reentry. Em moves towards depolarization. Gradual depolarization means more Na+ in activation gates close.

Pacemaker cell: Decreases automaticity. Em shows little or no depolarization and may even more toward hyper polarization.

Hypokalemia:
Non-pacemaker cell: increases conduction velocity
Pacemaker cel: increases automaticity, ectopic pacemakers!!

Antiarrythmic drug: probably never accelerates "normal" pacemaker depolarizations in ectopic pacemakers, but drugs that prolong the AP can cause early afterdepolarizations and tornado via triggered automaticity. Drugs that reduce the depolarizing phase 0 currents can facilitate reentry circuits in regions where conduction is already marginal for any reason (ischemia, etc). Thus a slight additional depression of conduction could allow reentry of an impulse around a damaged Purkinje fiber branch point and set up a stable reentrant focus with ventricular tachycardia.

Hint 4

Permeability has a big effect in pacemaker cells because K+ permeability is usually very low. The reverse is true for non-pacemaker cells.