PBL 4 - membrane excitability Flashcards
where is K+ most abundant?
inside cells (98%) — only 2% in extracellular fluid/blood plasma
what is the normal range of K+?
3.5-5mM
what are 2 the terms used to describe when the K+ gradient is disrupted?
1) hyperkalemia
2_ hypokalemia
what are some causes of hyperkalemia?
- excessive intake
- decreased renal removal (renal failure, adrenal disease, medications eg. ACE inhibitors or NSAIDs)
- tissue damage and release from stores
what are the effects of hyperkalemia?
- impairment of neuromuscular, GI and cardiac systems — can cause fatal cardiac arrhythmias
what awful cardiac arrhythmia can hyperkalemia cause?
ventricular fibrillation — abnormal electrical activity causes quivering ventricles — medical emergency as can go into asystole within seconds
what are some causes of hypokalemia?
usually excess K+ loss in urine (diuretics, vomiting, diarrhoea, kidney disease)
what are the effects of hypokalemia?
- cardiac problems — arrhythmias
2. skeletal muscles dysfunction — myalgia, muscle cramps, respiratory depression
what determines cellular excitability?
membrane potential of the cell
what is the membrane potential largely determined by?
the gradient of K+ across the cell membrane
what does the Nernst equation describe?
how the gradient of K+ can affect the membrane potential
what does this ECG show?
ventricular fibrillation
what does this ECG show?
ventricular tachycardia
what symptoms do people with hypokalemia present with?
weakness and fatigue
how do ions such as K+ cross a cell membrane and why?
through ion channels as lipid bilayers of the cell membrane have a low permeability to charged ions
what are the 2 types of membrane-spanning proteins?
ion channels and ion pumps
what are the key differences between ion channels and ion pumps?
- ion pumps — use ATP — pump ions across membrane — create ionic gradients
- ion channels — don’t use energy — important in setting membrane potential and action potential
label this ion channel
what is the purpose of the ion selectivity filter?
only lets a certain ion travel through
what is the purpose of m (activation) gates and h (inactivation) gates?
allows the ion channel to open at the suitable time — when the m gate opens, ions travel through before the h gate closes
what causes the m gate to open?
when an AP comes along in an excitable cell, it depolarises the cell causing the gate to open
what happens at the same time as the ions start to enter the ion channel?
h gate starts to close — closure is very slow
when is the ion channel said to be inactive?
when the h gate is closed
what is another name for the inactive state of the ion channel?
refractory
what needs to happen for the ion channel to open back up again and when does this occur?
h gate needs to be open for the channel to be open — happens when the cell goes back to its RESTING MEMBRANE POTENTIAL
describe the basic structure of sodium, calcium and voltage-gated potassium channels
- made up of 4 subunits
- each subunit has 6 transmembrane domains S1-S6
- S1-S6 are connected by a series of intra + extra cellular loops
which transmembrane domain in the subunit is the putative voltage sensor (m gate)?
S4
what is the link called between S5 and S6 and what is its role?
pore-forming loop —forms pore or hole through the membrane = where ions travel
what is the h gate in terms of the subunits in the membrane?
the link between the 3rd and 4th subunit = inactivation (h) gate