1.4. Classification, function and main features of ion channels. Voltage-gated Ca2+ channels. Cellular calcium metabolism. Flashcards
I. Classifications of ion channels
1. What are the 3 classifications of ion channels?
1/ Based on ion charge
2/ Based on cellular localization
3/ Based on gating mechanism
I. Classifications of ion channels
2. What are the characteristics of “Based on ion charge” ion channels?
Channels lined with (+) charges permit anions, with (-) charges permit cations
I. Classifications of ion channels
3. What are the characteristics of “Based on cellular localization” ion channels?
1/ plasma membrane channels: Na+ -, Ca2+ -, K+-channels
2/ intracellular channels that are classified according to the location of the channels (ex: ER channels – RyR, SERCA)
I. Classifications of ion channels
4. What are the 5 types of ion channels based on gating mechanism?
1/ Voltage-gated channels
2/ Ligand-gated channels
3/ Mechano-sensitive channels
4/ Second messenger-gated channels
5/ Heat/light-sensitive channels (less important)
I. Classifications of ion channels - based on gating mechanism
4A1. Characteristics of voltage-gated channels
1/ Activated by changes in the electrical membrane potential near the channel (usually activated by depolarization, but sometimes by hyperpolarization)
- Membrane potential alters the conformation of the proteins – opening + closing
2/ Important role in excitable (neuronal/muscular) cells for rapid + coordinated depolarization
I. Classifications of ion channels - based on gating mechanism
4A2. Examples of voltage-gated channels
1/ Na+ channels for threshold-activated depolarization phase in neuronal APs, have both a fast activation + slow deactivation gate sensitive to depolarization, which accounts for the timing and shape of the AP
2/ K+channels for repolarization phase in AP
3/ Ca2+ channels, e.g., at synaptic terminals to trigger NT release
4/ Inward-rectified K+channel (KIR) – allows for K+- leakage out of the cell only at very negative membrane potential (~-90mV)
I. Classifications of ion channels - based on gating mechanism
4B1. Characteristics of Ligand-gated channels
1/ Activated in response to the binding of a chemical messenger (ligand)
2/ Ligands can be lipids (ex: PIP2), cyclic nucleotides (cAMP), NT (ACh)
3/ Sensors on extracellular side of the membrane (often found in in the synaptic membrane and neuromuscular junctions)
I. Classifications of ion channels - based on gating mechanism
4B2. Examples of Ligand-gated channels
nAChR on skeletal muscle that opens in response to ACh binding and allows cations (Na+/K+) through
I. Classifications of ion channels - based on gating mechanism
4C1. Characteristics of Mechanosensitive channels
Sensitive to the level of tension in membrane and activated by the deformation
I. Classifications of ion channels - based on gating mechanism
4C2. Examples of Mechanosensitive channels
Examples: ones that are found in the cochlear hair cells and on certain touch receptor cells in the skin
I. Classifications of ion channels - based on gating mechanism
4D1. Characteristics of Second messenger-gated channels
1/ Controlled by changes of intracellular signaling molecules (ex: cAMP, IP3)
2/ Sensors on intracellular side of the membrane
I. Classifications of ion channels - based on gating mechanism
4D2. Examples of Second messenger-gated channels
IP3-receptor on the Sarcoplasmic reticulum (SR) that is activated by IP3
I. Classifications of ion channels - based on gating mechanism
4E. Examples of Heat/light-sensitive channels
1/ Light: channel ‘’rhodopsins’’ in the eye
2/ Heat: TRPV1 for sensation of heat in skin q
II. What are functions of ion channels
1/ Establishing a resting membrane potential
2/ Builds electrical signals (action potential) by gating the flow of ions
3/ Controlling the flow of ions across a membrane
4/ Regulating the volume
III. What are features of ion channels
1/ Arrow, highly specific transmembrane protein pores on the membrane
2/ Passive diffusion: permit diffusion of ions down their electrochemical gradient when open
3/ Gated: a conformational change can be induced to open/close the pore
4/ Selective based on ion charge and ion size
5/ Fast transport – about 4 orders of magnitude faster than carriers (106 – 108 ions/sec)
6/ It cannot really be saturated at normal physiological concentrations (unlike carriers who can be saturated)
IV. Ion channels - EXTRA
1A. The role of non-specific cation channels
1/ Can transport Na+, K+, (some of them also Ca2+) ions
2/ Depolarizes the cell
IV. Ion channels - EXTRA
1B. The mechanism of non-specific cation channels
1/ Opening of non-specific cation channels depolarizes the cell
2/ Under resting conditions, Na+ influx dominates, K+ efflux is much smaller because of the small driving force
3/ Driving force: the membrane potential minus the equilibrium potential of the particular ion
(Em-EK ~ +10mV
Em-ENa ~ -130 mV
Em-ECa ~ -190 mV )
IV. Ion channels - EXTRA
2. The role and mechanism of Cl- channels
1/ In the majority of the cells Em ~ ECl, -> accordingly the driving force for Cl-=0 Therefore opening of the channel under resting conditions results in no ionic current.
=> There are exceptions (e.g. epithelial, smooth muscle cells and some neurons) in which chloride equilibrium potential is more negative than the membrane potential (in this case Cl- channel opening hyperpolarizes)
2/ However, during depolarization of the cell (Em changes), removes from the equilibrium, accordingly, high Cl- conductance counteracts depolarization:
3/ Regulation of Cl- channels:
- Ligand-gated (e.g. GABAA- and glicin-receptors)
- Ca2+-activated
- cAMP-activated (e.g. CFTR)
- mechanosensitive
V. Voltage-gated Ca2+ channels
1. What are characteristics of voltage-dependent Ca2+ channels?
- Their structure is similar to that of voltage dependent (Na+) channels
- Not only depolarizes the cell but during its activity, cytoplasmic [Ca2+] also increases -> Ca2+ signal generation
V. Voltage-gated Ca2+ channels
2. What is the mechanism of voltage-dependent Ca2+ channels?
Their activation augments depolarization -> it is a self reinforcing process, results in action potential generation or contributes to the depolarizing phase of an action potential or can result in prolonged depolarization
V. Voltage-gated Ca2+ channels
3. What is the purpose for classification of Voltage-gated Ca2+ channels?
Purpose of this classification: there are various types which differ in their…
1/ Threshold potential
2/ Speed of inactivation
3/ Conductance
4/ Regulation
5/ Pharmacology
V. Voltage-gated Ca2+ channels - Classification of voltage-dependent Ca2+ channels
- What are the 5 types of voltage-dependent Ca2+ channels?
L-type
T-type
N-type
P-type
R-type
V. Voltage-gated Ca2+ channels
4A. Location, function and activation voltage of L-type VG Ca2+ channels?
1/ Location: Skeletal + SM, ventricular myocytes
2/ Function: Cardiac AP Plateau, skeletal + SM contraction
3/ Activation voltage: High
V. Voltage-gated Ca2+ channels - Classification of voltage-dependent Ca2+ channels
4B. Location, function and activation voltage of T-type VG Ca2+ channels?
1/ Location: SA node
2/ Function: Pacemaker activity
3/ Activation voltage: Low
V. Voltage-gated Ca2+ channels - Classification of voltage-dependent Ca2+ channels
4C. Location, function and activation voltage of N-type VG Ca2+ channels?
1/ Location: Brain and PNS
2/ Function: Synaptic NT vesicle release
3/ Activation voltage: High
V. Voltage-gated Ca2+ channels - Classification of voltage-dependent Ca2+ channels
4D. Location, function and activation voltage of P-type VG Ca2+ channels?
1/ Location: Cerebellar cells
2/ Function: N/A
3/ Activation voltage: High
V. Voltage-gated Ca2+ channels - Classification of voltage-dependent Ca2+ channels
4E. Location, function and activation voltage of R-type VG Ca2+ channels?
1/ Location: neurons
2/ Function: N/A
3/ Activation voltage: intermediate
VI. Cellular Ca2+ metabolism
1. What are 2 important channels in Cellular Ca2+ metabolism? What is their mechanism?
- ORAI1 is a Ca2+ release-activated Ca2+ channel protein 1
- STIM1 is so called “stromal interaction molecule 1”
Mechanism:
- STIM1 senses a decrease in [Ca2+]ER, and activates ORAI1 in the plasma membrane
- ORAI1 mediates Ca2+ influx following depletion of intracellular Ca2+ storage and channel activation by the Ca2+ sensor STIM1
- Increase in cytoplasmic [Ca2+] with open Ryanodine Receptor => release even more Ca2+ into cytoplasm
VI. Cellular Ca2+ metabolism
2. What is the concentration of Ca2+ in ER?
10^-3 M
