Flashcards in Drugs modifying cardiac rate and force Deck (101)
what are the regulatory influences on heart rate?
- balance of autonomic input
- blood pH
- thyroid hormones
what is overdrive suppression?
the SA node sets the rhythm for the heart because it discharges APs at a greater frequency than AV and his system
what four currents are important in the phase 4 (pacemaker potential ) of SA and AV nodes?
Ib - background sodium current inward
increased funny current - HCN channels open to conduct Na and K inward
ICaT - transient inward calcium current
and decreased Ik - delayed rectifier potassium current
why is it called the funny current?
The inward movement of Na and Sodium is mediated by hyperpolarisation and cyclic nucleotide gated (HCN) channels
what is the sequence of channel opening in
immediately after AP the membrane potential reaches its most negative value this is enough to open channles that conduct NA and K
then I cat switches on just before we hit threshold
at this point another class of VA channels opens
what mediates phase 0 of nodal AP?
increased Ical - long calcium current
what mediates phase 3 - downstroke of nodal AP ?
increased Ik - delayed rectifier potassium current
what current/ s mediated phase 4( diastolic potential) of atrial and ventricular myocyte APs ?
Ik1 - inward rectifier potassium current - this steady membrane potential is determined by a constant trickle of K ions OUTWARD
what does the outward trickle of K in phase 4 of atrial and ventricular myocyte APs result in?
the activation of VA I na - this is responsible for upstroke.
the majority of Na channels do not remain conducting for long. They go into a _____ _______ state after a millisecond.
the majority of Na channels do not remain conducting for long. They go into a nonconducting inactivated state after a millisecond.
what is responsible for the small flux after upstroke in atrial and ventricular myocyte APs ?
due to a combination of
1. Na ceasing
2. Ito - a transient outwards potassium current
what mediates phase 2 (plateau) in atrial and ventricular myocyte APs?
1. Increased CaL - long calcium current (inward)
as this happens K channels are slowly activated so the plateau is a fine balance of inward Ca movement by outwards K movement.
what two other mechanisms support phase 2 of atrial and ventricular myocyte APs?
1. not all VA Na inactivate - about 1% remain open and this gives rise to INaL - this is a late (or persistent) sodium current inward.
2. This is not an ion channel but a transporter. The Na Ca exchanger. This is in several forms in the body but it is NX1 in the heart. At resting potential it allows 3Na in and expells 1 Ca - this Ca has a +2 charge though! If, however, the MP is at depolarising potential this transporter will run backwards.
what mediates phase 3 of atrial and ventricular myocyte APs?
Ik - there are two components
- a fast activating one fast I kr which opens first
- a slow activating one - Iks
Noradrenaline (postganglionic transmitter) and adrenaline (adrenomedullary hormone) activate _____ in nodal cells and myocardial cells to sympathetic system
B1 adrenoceptors are __ coupled. The__ protein that they couple to is __. This is a stimulatory_ ____ which activates the membrane enzyme _____ _____ which in turn generates ____ from ATP.
B1 adrenoceptors are G coupled. The G protein that they couple to is Gs. This is a stimulatory G protein which activates the membrane enzyme adenylyl cyclase which in turn generates cAMP from ATP.
what happens to the heart rate when sympathetic system is stimulated?
increase HR - a positive chronotropic effect
what two things happen to increase AP rate?
i) increase in the slope of phase 4 depolarisation
ii) reduction in the threshold for AP initiation
what mediates the increase in the slope of phase 4 depolarisation from sympathetic stimulation?
increased If and ICa
what mediates the decrease in threshold of phase 4 depolarisation from sympathetic stimulation?
I Ca - Because inward Ca is stimulated this means that the pacemaker potential reaches threshold at a more negative value than usual.
what other things happen to the heart on sympathetic stimulation?
1. increased contractility
2. increased conduction velocity
3. increased automacity
4. decreased duration of systole
5. decrease in cardiac efficiency
6. increased activity of the Na/ K ATPase
7. increased mass of cardiac muscle
what causes the increased contractility from sympathetic stimulation ?
i) an increase in phase 2 of the cardiac action potential in atrial and ventricular myocytes and enhanced Ca influx and
(ii) sensitisation of contractile proteins to Ca
what causes increased conduction velocity in AV node in sympathetc stimulation?
due to enhancement of If and I ca (as in SA node) This occurs because of the calcium flux in the AV node is increased
what causes increased automacity in sympathetc stimulation? (i.e. tendency for non-nodal regions to acquire spontaneous activity – explored in later
If the muscle cells are stimulated hard then even muscle cells can discharge AP at their own rhythm i.e. without SA control
this leads to ventricular fibrillation- very dangerous
what causes a decrease in the duration of sytstole in sympathetic stimulation
due to cAMP due to increased uptake of Ca2+ into the sarcoplasmic reticulum
why is there also a decrease in the duration of diastole in sympathetic stimulation?
the rate of relaxation must also increase because if it didnt then the ventricles would be partially filled with blood before the next filling.
there is also a decrease in cardiac efficiency in sympathetic stimulation with respect to____ consumption which increases disproportionately with increasing work
there is also a decrease in cardiac efficiency in sympathetic stimulation with respect to oxygen consumption which increases disproportionately with increasing work
Parasympathetic fibres are stimulated by the____ nerve.
_____ is the postganglionic transmitter and it activates ________ largely in ___ cells.
Parasympathetic fibres are stimulated by the vagus nerve.
Acetylcholine is the postganglionic transmitter and it activates M2 muscarinic cholinoceptors largely in NODAL cells.
It is the ____ and ____ subunits that are important in the cardiac regulation of the parasympathetic system
It is the beta gamma subunits that are important in the cardiac regulation