´Ion channel proteins´Contain polar R groups and nonpolar R groups
´Polar R groups at either end exposed to watery cytosol or water extracellular fluid
´Nonpolar R groups in the center, interacting directly with lipid bilayer
´Ion selectivity - each channel is specific to which ions can flow in and out
´Driven by nature of subunits
´Pore size (think about ion sizes)
´Gating - open, closed, inactive
´Driven by changes in surrounding cell membraneIon pumps´- another protein facilitating ion movement across membrane (active transport)
´Move substances AGAINST concentration gradient
´Formed by membrane-spanning (transmembrane) proteins
´Use energy from ATP breakdown
´Important in neuronal signalling by moving Ca2+ and Na+ out of cell
´Famous example: Na+/K+ ATPaseDiffusion´passive movement of ions
´Dissolved ions distribute evenly
´equilibrium
´Ions flow down concentration gradient when:
´Channels are permeable to specific ions
´Concentration gradient exists across the membrane´Electricity´Electrical current (I) is the movement of charge, can be driven by ions.
´Measured in amperes (amps)
´Influenced by two factorselectrical current influenced by´1. Electrical conductance (g) - relative ability of charge to migrate from point A to B
´Resistance (R)
´R = 1/g
´2. Electrical potential (voltage) - force exerted on charged particle
´Difference in charge between cathode and anode
´OR difference in charge between intracellular and extracellular fluids (aka across neuronal membrane)
´Greater the voltage, greater the flow of ions (or charge)´Electrical current flow across a membrane
Ohm's law I =´gV
´Current (I) is driven by conductance (g) times the difference in voltage (V)
´Ions will not move if conductance is zero
´No matter how great difference in charge is
´Must have channels to make membrane permeable to that ionMembrane potential´voltage across the neuronal membrane at any moment
´Denoted Vm, measured in millivolts (mV)
´Can be measured by microelectrode
´Contains thin glass tube that can penetrate membrane
´Wire on outside of cell
´Connected to voltmeter
´Measured difference between outside and inside of cell´Resting membrane potential of a typical neuron is about-65mVequilibrium potential (Eion)´- electrical potential that exactly balances the ionic concentration gradient
´Occurs when the tendency of an ion to move due to its concentration gradient is EQUALLY balanced by the tendency of that ion to move due to it's electrical potential (ie, the point at which no movement occurs)
´Despite large concentration gradient of K+, no net movement of ions when separated by a phospholipid membrane without ion channels
´Vm = 0 because K+:A- ratio = 1 on both sides of membrane
´K+ channels allow selective movement of K+, not A- along concentration gradient
´Inside of cell becomes more negative
´Charge difference across as membrane (electrical potential, Vm) pulls K+ back inside cell
Equilibrium reached with K+ channels in the phospholipid bilayer when forces driven by electric and concentration gradient are balanced on either side of membrane´Equilibrium potential—(cont.)
´Four important points´Large changes in Vm driven by minuscule changes in ionic concentrations
´Net difference in electrical charge occurs at inside and outside membrane surface
´Rate of movement of ions across membrane is proportional to differences in membrane and equilibrium potential (Vm - Eion)
´If concentration difference is known for ion, equilibrium potential can be calculated for that ion.´The distribution of ions across the membraneCl- more concentrated on inside, ´K+, Na+ and Ca2+ more concentrated outside•Membrane potential depends on ionic concentrations on both sides of membrane•Driven by ion pumps
•Na+/K+ pump
•Hydrolyzes ATP in presence of Na+
•3 Na+ out, 2 K+ in
•Ca2+ Pump
•Hydrolyzes ATP to move Ca2+ against concentration gradient, out of cell
•These pumps work constantly to maintain concentration gradients to ensure normal physiology´Equilibrium potential—(cont.)´Inside positively charged relative to outside´The Nernst equation´Calculates the exact value of the equilibrium potential for each ion in mV
´Takes into consideration:
´Charge of the ion
´Temperature
´Ratio of the external and internal ion concentrationsThe sodium-potassium pump´An enzyme that breaks down ATP when Na present
´Calcium pump actively transports Ca2+ out of cytosol.´Relative ion permeabilities affect the membrane at rest´Neuronal membranes permeable to more than one type of ion.
´Membrane permeability to different ions determines membrane potential.
´Goldman equation
´Takes into account permeability of membrane to different ions
´This equation can be used to calculate resting membrane potential, NOT the Nerst equation´Relative ion permeabilities of the membrane at rest—(cont.)
Selective permeability of potassium channels´—a key determinant of resting membrane potential
´Determined by the amino acids that line the pore of the channel
´Many types of potassium channels
´Lily & Yuh-Nung Jan: amino acid sequences, family of K+ channels
´Example: Shaker potassium channel´Relative ion permeabilities of the membrane at rest—(cont.)
K+ channels´four subunits
´Channel selectively permeable to K+ ions
´MacKinnon—2003 Nobel Prize
´Mutations of specific K+ channels; inherited neurological disorders´Import to regulate external K+ concentration´Resting membrane potential is close to EK because it is mostly permeable to K+.
´Membrane potential extremely sensitive to extracellular K+
Increased extracellular K+ depolarizes membrane´Relative ion permeabilities of the membrane at rest—(cont.):
´Because membrane potential is so sensitive to K+, mechanisms evolved to regulate the external potassium concentration:´Blood-brain barrier
´Walls of brain capillaries limits movement of K+ into extracellular space of brain
´Astrocytes play major role in K+ buffering
´Contain K+ pumps to remove K+ from extracellular space
´Called potassium spatial buffering
´Elevations in blood K+ can have serious consequens
