Lecture 19: Membrane Potential and Electrophysiology of the Heart Flashcards
Two critical qualities of plasma membrane
- Capacity to maintain ion gradient between icf and ecf
- Capacity to respond to a wave of depolarization by briefly opening and closing specific channels which influence the contractile performance of the heart
Resting membrane potential voltage
-90 mV
The Na/K pump is inhibited by
Cardiac glycosides
Ex. digoxin
Cardiac glycosides increase…
used to treat…
the contractibility of the heart and are widely used to treat heart failure
Cardiac glycosides are commonly called
digitalis glycosides because most come from digitalis (foxgrove) plant
Cardiac glycosides influence Na/K flow in cardiac muscle, increasing the contraction of
the atrial and ventricular myocardium (positive inotropic action)
5 steps of cardiac glycoside mechanism
- Inhibition of the Na/K pump cell membrane
- This cause an increase in intracellular Na+ concentration, altering the Na+ gradient across the cell membrane
- Inward directed Na+ down the concentration decreases leading to a decrease in the Na-Ca exchange activity
- As less Ca is pumped out of the cell by Na/Ca exchanger, the intracellular Ca concentration increases
- Since tension is directly proportional to the intracellular Ca concentration, cardiac glycosides produce an increase in tension by increasing the intracellular Ca concentration - a positive inotropic effect
Ca ATPase
- Assists with Ca extrusion from the cell
- Seems to be involved in maintaining diastolic cytostolic calcium concentration
Na-Ca exchanger
- Na flows inward along its electrochemical gradient
- Ca flows outward against an electrochemical gradient
- Major mechanism of Ca extrusion through the plasma membrane into the extracellular fluid
What allows the myocardium to relax during repolarization
Ca pump of SR and NA/Ca exchanger lowers the cytoplasmic Ca concentration
In heart muscle, it seems that adrenergic stimulation acts via their receptors on the same channel depolarization acts on because
no amount of adrenergic stimulation will open the Ca channels in the absence of an accompanying voltage stimulus
Voltage gated channels in the heart
- Entry of extracellular Ca activates Ca sensitive release channels (ryanodine channels) in the SR through which stored Ca flows into the cytoplasm
- A rapid increase in intracellular Ca occurs and tension starts to develop (calcium induced calcium release)
Tetrodotoxin
Inhibits Na channels, resulting in a decrease in excitability of the heart
Vermapamil
Calcium channel blocker
Antiarrhymythic drugs
Ca channel blacokers that decrease Ca entry into the cell resulting in a decreased rate of contraction
Four examples of adrenergic agonists
- Dopamin
- Dobutamine
- Amrinone
- Milrinone
Dopamin and dobutamine
- Positive inotropic agents
- Used to treat heart failure
Amrinone and milrinone
- Inhibitors of phosphodiesterase which hydrolyses cAMP
- Used to treat heart failure
Autorhythmicity
Heart beats rhythmically due to it’s ability to create action potentials
Two types of specialized cardiac cells
- Contractile cells
2. Autorhythmic cells
Contractile cells
99% of cardiac muscle cells that do the mechanical work of pumping. They don’t initiate their own action potential
Autorhythmic cells
- Remainder of cardiac cells. Small and do not contract
- Initiate and conduct action potentials responsible for contraction of the working cells
Autorhythmic cells action potential
- Have no resting membrane potential
- Display pacemaker activity
Ions involved in autorhythmic action potential
- Decrease in K efflux
- Ib: Constant Na influx via Na leak channels
- If: Pacemaker current. Na influx via voltage-dependent Na channels
- Ca: Brings the membrane potential to threshold
What is the basis for the pacemaker potential
Ifunny
Ifunny is called the
pacemaker current
Ifunny is activated by
increasing negative voltages
Ifunny is carried by
Na via voltage-dependent Na channels
Ifunny channels are opened when
membrane potential becomes more negative than -50mV
Sympathetic stimulation does what to Ifunny
Increases number of open channels leading to an increase in heart rate
Parasympathetic stimulation does what to Ifunny
decreases the number of these open channels leading to decrease heart rate
Phase 0 of Pacemaker potential
Depolarization: inward Ca carried by L-Ca channels
Phase 3 of pacemaker potential
repolarization: K efflux
Phase 4 of pacemaker potential
Spontaneous depolarization. Accounts for automaticity of SA nodal cells
What sets the heart rate?
Rate of depolarization
