Intro to Electrophysiology Flashcards
A voltage difference or separation of charge between the internal and external surfaces of the plasma membrane
Membrane potential
At rest, the membrane is
Polar
In general, the internal surface region of the plasma membrane has what charge?
Negative
In general, the extracellular surface region of the plasma membrane has what charge?
Positive
The inner surface of the plasma membrane is negative relative to the
-does not mean it is loaded with negative charge
Extracellular surface
The resting membrane potential of a large nerve is maintained at approximately
- 90 mV
- means inner membrane is 90 mV less positive than outer
The flow of charge (ions)
Current
The resting membrane potential is due in large part to the membrane distribution of
Na+ and K+
Located inside the cell and help establish the resting membrane potential
Negatively charged proteins and Cl-
Generated any time an ion translocates across the cell membrane
Current (I)
Cell and tissue function is controlled by
Ion flux
In a resting motor neuron, there is a high intracellular concentration of K+ as compared to a high extracellular concentration of
Na+
Because of its chemical concentration gradient, there is a strong driving force for the translocation of K+ out of the cell through
K+ leak channels
Na+ and K+ are moved across the membrane against their concentration gradients by the
-maintains net negative charge on inner face of membrane
Na+/K+ ATPase (3 Na+ out, 2 K+ in)
How many ATP molecules are used during each ATPase cycle?
One
The tendency for an ion to move in one direction or another
Electromotive Force (EMF)
Dependent on the intra- and extracellular concentrations of Na+, K+, and Cl-, as well as membrane permeability of these ions
EMF
By maintaining RMP at around -90 mV, there exists a tremendous electrochemical gradient for the movement of Na+ inward, which is the defining characteristic of
Membrane depolarization during action potential
What are four electrogenic tissues that are dependent oupon anions (Cl-) and cations (Na+, K+, Mg2+, and Ca2+) for electrogenecity?
Heart, Skeletal muscle, Neurons, Vascular smooth muscle, and GI smooth muscle
The resting membrane potential is set by the membranes concentration gradient for
K+ out of the cell
The larger the K+ concentration gradient (i.e. the ratio of intracellular K+ to extracellular K+), the greater the
Nagtivity in the cell
When the the plasma [K+] is elevated (i.e. during hyperkalemia), the concentration gradient across the cell membrane is lowered; and this drives the
Resting membrane potential to be less negative (Membrane depolarizes)
Neurons communicate via the electrochemical phenomenon known as an
Action potential
The plasma membranes of neural and muscle cells contain voltage-gated Na+, K+, Cl-, and/or Ca2+ channels that open/close when there is a specific change in
Membrane potential
Causes the initial upward phase of the action potential (membrane depolarization)
Na+ flux
The action potential can be recorded and measured as
Electric current (INa+)
Rapid (< 0.1 msec) changes in membrane potential that result from alterations in the permeability of the membrane to Na+ and K
Neuronal Action Potentials
What are the three phases of the action potential?
- ) Resting
- ) Depolarization
- ) Repolarization
When the nerve fiber is at resting membrane potential
Resting phase
Characterized by acute changes in the membrane potential, which result in increased permeability of the plasma membrane to Na+ due to inactivation of resting voltage gated Na+ channels
Depolarization phase
Describe the depolarization phase of an action potential
Na+ rushes into the cell through open (active) Na+ gated channels, this results in the membrane potential becoming less negative, and more Na+ channels are activated, thus increasing influx of Na+
The membrane potential at which I-Na+ overcomes any opposing forces to inward I-Na+ and I-Na+ becomes self-reinforcing rapidly driving membrane potential toward the Nernst equilibrium potential for Na+
Threshold potential (Usually around -70 - -60 mV)
The changes in membrane potential resulting from depolarization induce the opening of
Voltage-gated K+ channels
Peak opening of the voltage gated K+ channels has occured at around
60 mV
What happens during the Repolarization phase?
Na+ channels close, but K+ channels remain open for a while allowing the membrane potential to become more negative. Then Na+/K+ ATP restore the resting membrane potential
Voltage-gated Na+ channels have 2 gates in series.
- ) One is located more toward the extracellular side and is called the
- ) One is located more towards the cytoplasmic side and is called the
- ) Activation gate
2. ) Inactivation gate
If either gate of the Na+ voltage-gated channel is closed, then the channel is
Inactive
What is the resting conformation of a Na+ channel?
Activation gates = closed
Inactivation gates = open
This specific conformation is important because Na+ channels can only be activated from the
Resting conformation
The majority of activation gates rapidly open in response to the
Threshold potential (about -60 mV)
During repolarization, both gates of the Na+ channel are
Closed (inactive conformation)
In the event of elevated extracellular K+
(i.e. severe enough hyperkalemia), RMP will be driven less negative; in so doing lessening the potential difference between
Resting membrane potential (RMP) and threshold
Decreasing the potential difference between RMP and threshold has what effect on neuromuscular tissue?
Makes them more excitable (irritable)
This excitability is very short lived because hyperkalemia depolarizes neuromuscular tissues and promotes inactivation of
Resting Na+ channels
-impedes generation of action potentials
Are comprised of a single gate
-possess both a voltage and time dependency
K+ Channels
During RMP, the gate is closed and the voltage-gated K+ channel is
Inactive (resting)
Upon depolarization to suprathreshold levels (> -60 mV), the K+ gate opens somewhat gradually, with the greatest percentage of K+ channels open around
60 mV
K+ channels change between conformations slowly. As membrane potential returns towards RMP, voltage-gated K_ channels remain open for several msec, resulting in a brief period of
Membrane Hyperpolarization
Another contributor to the generation of an action potential
Calcium
In cardiac myocytes and smooth muscle cells, the depolarization scheme is dominated by
Ca+ pumps/channels
By comparison to voltage-gated Na+ channels, voltage-gated Ca2+ channels are
Slow activating
What are the two important types of calcium channels?
L (long) type and T (transient) type
Activate and inactivate over more negative membrane potentials and therefore assist in the pacemaker function of the sinoatrial node
T-type channels
Have a high threshold for activation (> -30 mV), and sustain the plateau phase of the action potential found in cardiac myocytes and vascular smooth muscle
L-type channels
Under normal circumstances, any even that depolarizes membrane potential to threshold level will initiate an
Action potential
Not all depolarizations reach
Threshold
A subthreshold stimulus initiates subthreshold alterations in membrane potential by activating
-allows for Na+ influx
LIGAND-gated Na+ channels
Subthreshold changes in membrane potential are referred to as
-Proportional in amplitude to the stimulus strength
Graded potentials
Graded potentials can sum to reach
Threshold
The excitability of neuromuscular tissue is dependent upon the difference between
Resting potential (Em) and Threshold potential (Et)
= Em - Et
Another action potential can not be initiated when the Na+ channels are
Closed (inactive)
Period of time following peak action potential, where all voltage-gated Na+ channels are inactive (closed)
-extends until sufficient numbers of voltage-gated Na+
channels return to the resting conformation
Absolute refractory period
The recovery phase where enough Na+ channels have returned to resting that a relatively strong (suprathreshold) stimulus can initiate another action potential
Relative refractory period
Sodium that has entered the neuron (during depolarization) spreads to neighboring sections of the
Plasma Membrane
The migration of Na+ to neighboring sections of the plasma membrane induces which three things?
- ) Depolarization of adjacent regions to threshold
- ) Activation of restive voltage-gated Na+ channels
- ) The resultant action potential in adjacent areas of membrane
Thus, an action potential is propagated from the initial activation site, along the membrane, via a series of
Na+-induced depolarizations
Travel to the nerve terminus and/or soma and stimulate a response such as the release of neurotransmitters, or the opening of other types of voltage-gated ion channels (e.g., Ca2+ channels)
Action potentials
A phospholipid/cholesterol based substance that is formed by Schwann cells within certain types of neuronal tissue
Myelin
The presence of the myelin sheath prevents conductivity, hence AP are not generated within
Myelin
Within myelinated neurons, an action potential can only be generated within the
Nodes of Ranvier
Propagation of an action potential from node to node
-requires less energy than the cable-like conduction in non-myelinated neurons
Saltatory conduction
The maintenance of normal cardiac rate and rhythm is directed by the pacemaker activity of a population of electrogenic cells collectively known as the
Sinoatrial node
Undergo rythmic depolarization and repolarization in the absence of innervation
SA nodes
The concerted activities of T-type Ca2+ channels, Na+ HCN channels, and K+ channels enables inward ICa2+ and If (funny current = Na+) and outward IK+ within the
SA node
To begin one pacemaker cycle, inward ICa2+ and If, combined with outward IK+, enable a
Gradual depolarization
As the membrane potential creeps toward -55 mV, voltage-gated Ca2+ channels are increasingly activated, producing a rapid upstroke in
Action potential
T-type Ca2+ channels inactivate through the depolarization phase, and at about 0 mV HCN channels are inactivated, shutting down If, and thus allowing repolarization via
Ik+
Repolarization leads to a brief period of hyperpolarization which is necessary to reactivate
HCN channels
Relatively long duration APs which are named due to a characteristic plateau-shaped phase following depolarization
-ex: potentials regulating cardiomycete contractility
Plateau Potential
The plateau of the plateau potential is the result of K+ channels, which cause repolarization, being countered by
Ca2+ channels (activated by Na+ AP)
Somatic sensory receptors that mediate the pain signal
-activated during injury by factors such as bradykinin, substance P, etc
Nociceptors
The sensations of acute and chronic somatic pain are mediated by
Nociceptors
Nociceptor afferents (nerve fibers relaying into the central nervous system) consist of
Myelinated and unmyelinated fibers
The myelinated fibers are type Aδ fibers, which mediate the relay of so-called
Fast pain (Sharp/intense pain)
Working with type Aδ fibers are the populations of small diameter, unmyelinated, slow conducting pain afferents called
Type C fibers
Relay the sensation of dull, burning pain
Type C fibers
Pain afferents feed into the dorsal horn of the spinal cord and ascend specific tracts to the
Thalamus
Work by reversibly blocking action potentials in pain afferents
Local Anesthetics
In general these agents exist as weak bases (deprotonated) at physiologic pH (7.4), are lipid-soluble, and because of their hydrophobic nature preferentially
enter small diameter pain afferents
Local Anesthetics
Local anesthetic molecules are ionized by the acidic intracellular pH of the neuron, which enables them to bind
Voltage-gated Na+ channels (confers inactive conformation)
The process whereby action potentials are relayed between neurons and/or between neurons and affector tissues
Synaptic transmission
Neuromuscular transmission utilizes the neurotransmitter
Acetylcholine (ACh)
There are numerous neurotransmitters used for neuroneuronal transmission. The ubiquitous excitatory neurotransmitters are
Gluamate and aspartate
Common inhibitory neurotransmitters are
GABA and glycine
Chemical synaptic transmission is subcategorized into
Ionotropic and metabotropic
Utilizes neurotransmitters to activate ligand-gated ion channels residing in the post synaptic membrane
Ionotropic transmission
An example of an excitatory ionotropic system
-found in skeletal muscle
Nicotenic-cholinergice receptor (ACh = neurotransmitter)
What is faster, ionotropic or metabotropic transmission?
Ionotropic
Relies upon not only the release of chemical neurotransmitters, but the activation of receptor-mediated signaling in the effector tissue by the neurotransmitters
Metabotropic transmission
The AChmediated activation of cholinergic-muscarinic receptors within the sinoatrial node, which results in K= exiting the cell, used to control heart rate is an example of
Metabotropic transmission
Terminated by enzymatic dissociation of the neurotransmitters and/or re-uptake of the neurotransmitter by the pre-synaptic terminus
Neuronal Transmission
Can occur following the sustained stimulation of
neuronal transmission, such as what would occur in the presence of a cholinesterase inhibitor
Synaptic fatigue
Results from exhaustion of neurotransmitter reserves, desensitization of the postsynaptic receptors, and/or disruptions in local ionic gradients within the post synaptic neuron such that the stimulatory signal is dampened or terminated
Synaptic fatigue
ACh binding to the nicotinic-cholinergic receptor induces a conformational change in the channel receptor structure, which increases its permeability to
Na+, Ca2+, and K+
