L4: Cardiac electrical activity Flashcards
3 electrical properties of cardiomyocytes
-Excitability.
You have a resting membrane potential and something external to the cell causes it to depolarise to a threshold. When it reaches the threshold- trigger an AP.(similar to nerve cells)
-Conductivity
-Automaticity
where are fast-response AP cell found in the heart
-Found everywhere in the heart. Most common cell type in the heart->Most of the cardiomyocytes have a fast-response AP profile.
-there are also in specialised conduction systems
-these cells are essential to coordinate the very rapid spread of depolarisation through the heart, especially in the ventricle: the fast conduction pathways, ensures that depolarisation is tightly coordinated
what are ions involved at every stage of cardiac AP?
*electrochemical changes during cardiac AP.
Ions move down electrochemical gradient- create a current. Change over the time course of AP
Phase 0: Something happens to initiate the depolarisation in fast-response cells, the cell reaches a threshold -> triggers V-gated Na+ channels to open-> Na+ rushes in down the electrochemical gradient( fast influx of Na+)-Inward sodium current( iNa)- rapid +ve charge moving into the cells
Phase 1: Na+ channels close. ito= Transient outward- largely K+ current. K+ and Cl+ channels become activated-small repolarisation occurs.
Phase 2: Plateau.!!! Inward Ca2+ current, K+ channels open( move K+ out of the cells down the electrochemical gradient) and Na+/ Ca2+ exchanger- Na+ out, Ca2+ in.
Inward rush of Ca2+ very important !!for generating muscle contraction. Balance
iK channel opens. iK was activated right in the start (before and during depolarisation), but only start opening after a time delay. This time delay is modifiable- one of the ways the body can change the length of the plateau->this can change how much Ca2+ comes into the cell-> modifies the strength of contraction of the ventricles.
When iK opens-> outward K+ current->cell starts to repolarise in Nernst. As membrane potential drops- iK1 channels start opening ( switched off at higher membrane potential), iK1 channels take over again( as iK channels close).
Phase 4: Resting membrane potential. Largely dominated by permeability to Ca2+, not many other channels open at this point in the cycle.
*At rest these cells are mostly permeable to K+, so the membrane potential is close to the Nernst potential for K+.
what is nernst potential
The Nernst potential, also known as the Nernst equation or equilibrium potential, is a fundamental concept in electrochemistry and neuroscience. It describes the membrane potential at which the net flow of a specific ion across a membrane is zero, assuming that the membrane is selectively permeable to that ion.
The Nernst potential is calculated using the Nernst equation:
E = (RT/zF) * ln([ion]outside/[ion]inside)
The Nernst equation takes into account the concentration gradient of the ion across the membrane and the electrical charge of the ion. It predicts the equilibrium potential at which the electrochemical forces pushing the ion in one direction are balanced by the forces pushing it in the opposite direction.
The Nernst potential is particularly important in understanding the resting membrane potential of excitable cells, such as neurons and muscle cells. It provides insights into the membrane potential at which a specific ion (e.g., sodium, potassium, calcium) is in equilibrium and can help determine the driving force for ion movement during action potentials and other electrical signaling processes.
For example, the Nernst equation can be used to calculate the equilibrium potential for potassium (E_K+) in a neuron. Given the intra- and extracellular potassium concentrations, the equation can determine the membrane potential at which the net flow of potassium ions across the membrane is zero. This equilibrium potential for potassium is a crucial factor in establishing the resting membrane potential and influencing the excitability of the neuron.
change in ion current over the course of cardiac AP
electrogenic: meaning?
The term “electrogenic” refers to the generation or production of an electrical charge or potential difference across a cell membrane or within an electrochemical system. It indicates that a process or entity is responsible for creating an electric current or maintaining an electrical gradient
background activity during cardiac AP
Ca2+ ATPase( electrogenic-contributes to ion balances)- burns energy to move Ca2+ out of the cell. Need Ca2+ to contract but also need to remove Ca2+ to relax the cells.
Na+/Ca2+ exchanger- 3 Na+ come into the cell and 1 Ca2+ goes out. Can actually reverse which it does during the depolarisation phase. Contributes to either depolarisation or repolarisation of the cell at different points in the cycle.
Na+/K+ ATPase: 3-to-2 ratio. Electrogenic contribution.
difference between fast response and slow response AP cells
and clinical importance of it
!! Big difference:
upstroke. In fast-response cell it is near vertical. Big Na+ influx.
In slow response cells: Na+ does not contribute to the depolarisation of the cells, just Ca2+. Occurs on a slower time base, do not have the same massive electrochemical gradient driving Ca2+ into the cell as we have for Na+.
-Some of these cells do not have Na+ channels, some cells have the Na+ channels, but not as active. One reason for why the present Na+ channels are not that active- the resting membrane potential is much higher. Na+ channels are not reset. (need a certain degree of hyperpolarisation to reset to be able to open again)
Relevance: something can happen in the heart that can change the cells AP profile, e.g.: heart attack, blockage in the coronary artery, if cells are not adequately perfused they become metabolically challenged, might not have enough energy to get their membrane potential down to -80 mV. Fast-response cells can shift into slow-response type due to damage to cardiac tissue. This becomes functionally important: disturb the natural pattern of depolarisation-> arrythmias( part of the tissue not conducting depolarisation in the same way that it should be-> areas of recirculating currents-> arrythmia)
can heart be stimulated in ARP(absolute refractory period)?
no
Cardiac cells have a built-in safeguard: once they have depolarised cannot be activated again too quickly after. Heart has a range of frequencies at which the contraction is efficient.
can the heart be stimulated during RRP and SNP?
can stimulate the cells but it is a lot harder to do: might have to put a lot more current in. Takes more energy because not everything is reset: Na+ channels need to reset before they can fire again, so if stimulate during RRP> might only be able to activate half of the channels.> funny looking AP since only getting half as much depolirisation
importance of refractory period
!! Heart has to relax to fill with blood. Need a period where cannot stimulate the heart again- need refractory period- lets heart fill during diastole.
cardiac conductivity
Contraction in myocytes is generated by myogenic activation: cell-to-cell
Activity starts at SA node in the atrium-> spreads through the cells in the heart. Cardiac myocytes are physically connected via intercalated discs, which provide mechanical conductivity( pull on each other) and also electrical connectivity( ions can travel through the discs-> current travelling through the cardiac tissue via the junctions). This anatomical feature is central for the heart to depolarise in an appropriate sequence & produce coordinated contraction.
how does autonomic system act on SA node to change HR?
SA node is innervated by the autonomic nervous system:
-parasympathetic system acts on iach(Ach-signalling molecule for parasymp. System)> increases the K+ permeability of the pacemaker cells-> hyperpolarises the cells-> takes longer to get to threshold-> slow down HR
Sympathetic NS innervates the SA node directly as well
: release Noradrenaline> NA phosphorylates Ca2+ channels-> increases their opening potential> increases the slope of the pacemaker depolarisation> increase HR
how can HR be modulated using ion channels
Want to increase HR:
-increase the amount of inward current: open more funny channels-> faster depolarisation> reach threshold and reach AP earlier> faster HR.
*the opposite can be done if want to slow down HR
Want to slow down HR:
-open more K+ channels in phase 4: hyperpolarising the cell. Will take longer to reach threshold
The body can use both to alter HR
funny current
if= funny current. Na+ current. The funny current is activated by hyperpolarisation ( unlike other channels). As the cells hyperpolarise - funny current is turned on-> Na+ leaks in-> slow depolarisation.
currents during pacemaker AP
Currents:
iK current is on most of the time but varies in strength throughout the AP
iCa2+ current switches on and off
if= funny current. Na+ current. The funny current is activated by hyperpolarisation ( unlike other channels). As the cells hyperpolarise - funny current is turned on-> Na+ leaks in-> slow depolarisation.
