Excitable Cells: Resting Membrane and Action Potentials Flashcards
Examples of excitable cells
neurons and muscle cells
what do excitable cells do
generate action potentials that communicate information within and between cells via large transmembrane potentials
transmembrane potentials of excitable cells depend upon
- active transport of ions to maintain concentration gradient K+ and Na+ ions
- Presence of channels in cells plasma that = selective K+ ions
Na+/K+ ATPase
ATP-dependenttransporter that transports K+ and Na+ against their concentration gradients to maintain:
- low extracellular concentration K+
- high extracellular concentration Na+
Concentration of K+
High inside cell low outside cell
concentration Na+
Low inside cell high outside cell
Resting membrane potential
generated as K+ ions exit cell by flowing down concentration gradient through K+ selective channels
- in sekeltal muscle Cl- influx contributes to resting membrane potential
Cell excitation
Excitable cell fires action potential when depolarizing stimulus exceeds threshold for activation for Na+ and Ca2+ channels in membrane; ions flow into ell via energy of concentration gradient and make cell membrane potential transiently positive with respect to extracellular fluid space
repolarization occurs as threshold for activation voltage sensitive K+ channels exceeded and K+ ions flow out of cell
action potentials generated from
large negative resting membrane potential via excitable cells
resting membrane potential
membrane potential of excitable cell during interval between action potentials when net influx and efflux is =
RMP neurons and cardiac myocytes
largely due to K+; these ion channels =
RMP skeletal muscle
Cl- also important
generation of action potential involves
transient reversible changes in transmembrane potential from highly coordinated sequence of opening sea closing of voltage-gated ion channels that allow Na+ or Ca2+ influx to generate positive upstroke of action potential followed by K+ efflux which depolarizes membrane
Current
occurs as ions flow across cell membranes (flow of changes per second)
movement of charges
through ion channel pores is dwn electrical and ionic concentration gradients
Ohms law
describes flow of ionic current through membranes
V= IR
conductance
Inverse of resistance/ ability to flow
g=1/R
gV=I (Ohms law with conductance)
biological current is either
- ionic (carried by ions)
2. Capacitative (due to time-dependent differences in charge on 2 sides fo cell PM)
4 important ions for biological electricity
Sodium (Na+)
Potassium (K+)
Calcium (Ca2+)
Chloride (Cl-)
Flow of current in any electrical circuit requires
- Low resistance pathway (1/R)=g between two compartments
2. A driving force (V)
low resistance pathways
- (1/R)=g
- ion channel
- gap junction
- lower resistance of cytoplasm compared to PM (like when current flows w/ in a cell to other parts of cell)
driving force
- partly difference in concentration of ion between inside and outside of cell and partly electrical driving force that occurs when potential difference between two compartments
- electrical driving force can be across cell membrane or difference in potential at one pt of cell compared to another
intracellular and extracellular concentrations of Na+, Ca2+, K+ ions established by
active transport of Na+ out of cell and K+ into cell by electrogenic pump (Na+/ K+ ATPase); this does not make significant contribution to transmembrane potential of excitable cells
outside of cell
each cation assumed to be associated with like number anions outside cell (Cl-)
inside of cell
Cl- and mixture of impermeable anions
equilibrium potential
- plasma membrane is selectively permeable to K+ and K+ flows out of cell down its concentration gradient leaving Cl- and X- (impermeable anions) behind -> negative intracellular potential the negative potential attracts K+ and reduces is efflux; equilibrium potential is when the chemical force driving K+ out of the cell is offselt by the electrical force attracting K+ into the cell
Nernst equation
K+ equilibrium potential can be calculated this way ( so can other ions)
Ek= -61.5mV x (log10[K]I - log10[K]o)
Goldman-Hodgkin-Katz formulation resting membrane potential in words
- in essence this adds together forces for K+ flux, Na+ flux, and Cl- flux to determine RMP bit this takes into account differences in relative permiablity (P) for different ions and concentration of each ion inside and outside cell
resting membrane potentail
resting membrane potential = potential at which charges flowing into cell are balanced by net charges flowing out
- includes resting permeability to K+ ions and permeability of membrane to other ions in addition to K+ (in vertebrate skeletal muscle there is significant permiablity to Cl- ions at resting membrane potential)
Goldman- Hodgkin- Katz formulation resting membrane potentail formula
Vm= (-61.5mV)log10 [(Pk[K+]I + Pna[Na+]i + Pcl [Cl-]o)/(Pk[K+]o + Pna [Na+]o + Pcl[Cl-]i)]
membranes of all cells are
polarized
excitable cells are
hyper polarized, depolarized, depolarized as they perform their fnx
polarized
interior of cell is negative and exterior of cell is defined as 0mN or ground potential (excitable cells are in this state at rest)
hyperpolarized
additional positive charge is removed from cell (like when inhibitory neurotransmitter opens additional K+ or Cl- permeable channels the cell becomes more polarized or hyperpolarized
depolarized
positive charge is added to inside of cell and cell becomes less polarized (ie depolarized)
steps of action potential
- Depolarization
- Plateau potential
- Repolarization
- Absolute refractory period
- Relative refractory period
Depolarization
- Produces all-or none action potential if lg enough to exceed activation threshold of majority of voltage-sensitive Na+ channels in patch excitable membrane
plateau potential
varies from v brief (neurons) to v long (cardiac myocyte); its due to activation of voltage-gated Ca2+ channels
Repolarization
- return to resting membrane potential bc opening voltage dependent K+ channels that activate slower than Na+ channels
- allow K+ efflux via delayed rectifier channel current
after hyperpolarization
caused by in neurons Kvr (potassium voltage regulated?) channels stay active for short time after cell depolarized and membrane potential is moving toward Ek which = more negative than RMP
absolute refractory period
interval during which 2nd action potential can’t be triggered
relative refractory period
- interval during after-hyperpolarization when its possible to generate new action potential if new depolarization exceeds threshold of majority of voltage-sensitive Na+ channels in same patch excitable membrane as before
action potentials are
all or none events bc most Na+ channels open during upstroke of action potential and then inactivate (non-excitable closed state) to be available again cell membrane potential must return to negative resting potential so they can recover/ rest
voltage gated Na+ channel gates
m and h gate; m is on outside h is on cytoplasm side 3 states: - available - activated - inactivated
available
closed and non conducting (m closed h open)
activated
m and h gates open (open and conducting)
inactivated
m open, h closed (non conducting)
describe depolarization producing an action potential
stimulus depolarizes membrane from RMP toward AP threshold and positive charge of voltage sensor moves within protein wotward extracellular side channel -> activation gate (m) opening Na+ ions flow into cell open Na+ voltage dependent channel undergoes additional structural change closing inactivation (h) gate Na+ channel now inactivated and sodium is no longer entering the cell this -> absolute refractory period; the inactivated sodium channel will remain inactivated unless and until membrane potential eturns to negative potential close ot resting membrane potential (RMP must be negative long enough to allow voltage-gated Na+ channels to reset an available state)
absolute refractory period
the number of available voltage-gated Na+ channels is v important parameter for generating and propagating action potentials; if more than 50% of them in inactivated state the cell/ axon in absolute refractory period; in nerves and in the heart the direction of action potential propagates is determined in leg pt by being inactivated Na+ channels in one direction and available ones in other direction
relative refractory period
- if cell receives sufficiently lg stimulus before complete repolarization and there are enough Na+ channels available then another activation potential can fire during relative refractory period
excitatory post synaptic potentails
- physiological depolarizing stimuli for neurons = excitatory postsynaptic potentials
- these= produced by transient activation of neurotransmitter sensitive channels
- small depolarization EPSP -> few available Na+ channels in membrane opening imitating rapid flux Na+ ions into cell further depolarizing membrane -> increasing Na+ influx until membrane depolarizes to action potential threshold, generating upstroke of action potential
activation of Na+ channels during action prenatal is an example of
feed forward mechanism
repolarization occurs
due to an independent negative feedback pathway provided by activation of K+ conductance which = specific ion channel type (voltage-dependent delayed rectifier or Kvr channels)
does membrane potential arch ENa and why
no bc
- threshold for activation lev channels reached -> number K+ ions leaving cell increasing -> repolarization of cell membrane
- Na+ channels rapidly inactivate -> no reactivation unless membrane is depolarized to lg negative potential; repolarization occurs bc overall gK+ is much larger than it has been at resting membrane potential at end of action potential membrane potential briefly undershoots resting membrane potential (after hyperpolarization contributes to relative refractory period); AHP facilitates recovery of Na+ channel from inactivation
as hyperkalemia increases
Ek is less and less negative and Na+ channels remain inactivated for longer rendering neurons less excitable
cation redistrbution
- must have ability to redistribute cations to maintain electrochemical gradients that underlie ability of excitable cell to have large resting potential to generate action potentials otherwise repetitive generation of action potential would dissipate concentration gradients needs to control directional flow of ions
Na+/K+- ATPase or pump
- pumps sodium ions out and transports K+ into cell; exchanges 3 Na+ ions for 2 K+ ions; net loss of 1 positive charge from interior of cell
- this is essential for maintain concentration gradients that underlie the current flow required for resting potential and action potentials but does not have much of an effect on resting membrane potential which is mainly dependent on voltage independent K+ channels
transporters
- only indirectly related to RMP and APs bc they maintain ion concentration gradients
where are transporters directly important for maintaining membrane potentials
epithelial cells of kidney
without transporters maintaining ion gradients across cells
high flux ion channels would neither provide for the resting membrane potential nor would action potentials happen
calcium ion concentration gradient
in cardiac myocytes
- returned to extracellular space by ATP-driven Ca2+ pumps, or Ca2+-ATPases, and by exchange of intracellular Ca2+ for extracellular Na+
- the anti-porter mechanism fnxs bc the driving force from Na+ entry gradient into cell provides energy to drive Ca2+ efflux against concentration gradient for Ca2+ so Ca2+ exchange (Na+/Ca2+ exchanger) is indirectly ATP-dependent bc need ATP to move Na+ and the Na+ gradient in turn moves Ca2+
excitable cells generate all or nothing action potentials in response to
extrinsic stimuli
excitable cells have large negative resting membrane potentials which facilitate recovery of
voltage-gated Na+ and Ca2+ from inactivated states
action potential depends on
orchestration fo dfferent types ion channels opening and closing in precise sequence and opening is closing depends upon transmembrane electrical potential w/o voltage gated ion channels there are no action potentials
what is necessary for resting membrane potential
K+ and Cl- channels that don’t see transmembrane voltage
K+ flux
inwardly rectifying K+ channels in cardiac cells, always dependent on direction of K+ gradient; K+ always leaves cell bc intracellular K+ is always greater than extracellular K+ but how rapidly it leaves and how much leaves depends on steepness of gradient
Serum levels of Na+ and K+ during action potential
stay the same bc actually only need low levels of ions moving across membrane bc sensitivity of Na+/K+-ATPase to increasing extracellular K+
biological current flows between
2 compartments that are at different potentials when there is an open pathway such as:
- channels (made by transmembrane proteins)
- gap juncitons (formed between adjacent cells)
- membrane bound tubes filled with cytoplasm (axons ie neurons, and muscle cells)
pores allow ions to
flow down their chemical and electrical gradients
ions flow
between compartments when there is a permeable pathway
resting membrane potential is determined by
relative permiablity of cell membranes to different ions; the RMPs can be calculated using Goldman-Hodgkin-Katz equation
Resting membrane potentials are negative because
Pk and Pcl are relatively greater than Pna and Pca
ion concentration gradients in cells are maintained by
ATP dependent transport proteins
action potential
transient depolarization of membrane potential; requires depolarizing stimulus which is usually extrinsic but in case or pacemaker cells is inrinsic
steps of action potentials
resting potential -> threshold -> absolute refractory period -> relative refractory period -> resting state
sequential activation of ion selective voltage gated channels
threshold -> opening of Na+ channels -> opening K+ channels -> downstroke of action potential (bc of opening of K+ channels)
K+ channels closing
opening voltage-gated K+ channels depolarizes the membrane and the K+ channels close this is negative feedback cycle
smooth muscle in GI tract
doesn’t lead to all or nothing depolarization
depolarization phase
occurs due to large transient increase in membrane permiablity of Na+ or Ca2+ ions; repolarization occurs when permeability of K+ ions increases
Large negative RMPs
facilitate recovery of voltage-gated Na+ and Ca2+ from inactivated states
