K+ channels

• K channels are fast and selective
• Na doesn't form the same bonds with the replacement hydration shell, in the presence of high [Na] the pore collapses, if K+ is added back it will compete and the pore will open again
• consists of 4 identical subunits which all contribute to centrally located pore with spans membrane, each subunit contributes 2 helices and re-entrant loop to the pore region
• 4 binding sites for dehydrated K+, 8 oxygen atoms (4 above, 4 below): mimics hydration shell
• the energy for dehydration for Na is too high so it's easier to dehydrate K as its larger. It's easier to remove water molecules as they're further away from the nucleus
• bond distance between K and backbone carbonyls is the same distance as between K and hydrating waters. Na has larger distance between carbonyls, more energy to dehydrate, thermodynamically unfavourable
• K has more waters surrounding it than Na, which is just right for the channel
• backbone carbonyl oxygens react electrostatically with K+ ion and replicate oxygens from water
• contains a short pore region partially penetrating the membrane from exoplasmic surface
• there are 4 extended loops which are part of the 4 segments of the pore form the selectivity filter
• the selectivity filter is formed by a conserved sequence of amino acids "signiture sequence" which provides a favourable environment for potassium ions to pass through while excluding other ions
• voltage-sensing domains: respond to changes in membrane potential by undergoing conformational changes - allosterically regulate the opening or closing pore
• cytoplasmic domains: play role in channel assembly, regulation, and interaction with other proteins or signalling molecules
• K is allowed to be hydrated up to halfway through the membrane, the hydration shell is replaced with electrostatic interactions with the amino acids lining the pore
• helical dipole orients K up to the carbonyl oxygen. once it passes through it gets rehydrated
• channel open at low intracellular pH - high H+ conc, binding of H+ opens the gate, negatively charged amino acids will bind H+
• action potentials: resting voltage = -70mV, signal from nerve cell opens Na channel, change in voltage opens more Na channels, depolarisation down the axon, Na channels close, voltage-gated K channels open, hyperpolarisation, Na/K-ATPase resets gradients
• during action potential relatively positive on outside, paddle (structural element) move 'up' due to attraction of conserved Arg (+) residues to negative side of membrane