Nature of Neuronal SignalsGoing up = positive inside. Down = negative inside.Vm when one ion is permeableLeft – Only K+ is permeableRight - Only Na+ is permeableVm when several ions are permeableKey RulesIon Leakage and Na/K pumpsVoltage Gated Na channelsBISC 307L 2nd Edition Lecture 5Current LectureNature of Neuronal SignalsAll living cells generate an electrical potential difference (Vm) across their plasma membranes due to an unequal distribution of ions across the membrane because of selective permeabilityand transporters like the sodium potassium pump.Neurons and muscle cells are unique in that their electrical properties are used to generate signals in the form of brief changes in membrane potential. There are two general types of signals:1. graded/local signals. Graded because the size of the signal varies with the strength of the stimulus. And local because they are restricted to the point they originated from on the membrane. The amplitude exponentially decays with distance as it spreads away from the starting point, so it doesn’t get very far.2. all-or-none/regenerative signals. All-or-none because once the stimulus brings the Vm up to the threshold value, it causes a very fast, positive peak called the action potential whose amplitude is generally the same. Regenerative because as it spreads, it regenerates itself continually. No matter how long or big the axon is, once you generate an AP, it goes all the way to the end of the cell, undiminished in amplitude, until it hits the end where it stops. Stimulus = anything done to the cell that provokes a response, such as release of neurotransmitters, exposure to light, etc.Going up = positive inside. Down = negative inside. Vm when one ion is permeable2 important conditions behind the mechanisms of membrane potential:1. There is an unequal distribution of a particular ion across the membrane.2. The membrane of the cell has to be permeable to the ion (due to the presence of selective membrane ion channels)Left – Only K+ is permeablePotassium will diffuse outwards down its concentration gradient, leaving the inside of cell negative. Simultaneously, potassium also diffuses inwards down its electrical gradient, so you have a flux of potassium moving in two directions oppositely across the membrane. The rates ofmovement will continue until they reach equilibrium. At equilibrium, the flux of an ion down its concentration gradient will equal the flux of ions down its electrical gradient, and net movement will be zero. In membranes with only one ion permeable, equilibrium is achieved instantaneously. Right - Only Na+ is permeableNow we have a sodium selective channel. As sodium diffuses in down its concentration gradient, it makes the inside positive. As a result, Na also travels outwards down the electrical gradient. One way to calculate the membrane potential when only one ion is permeable is through the Nernst Equation. If a cell is only permeable to potassium, then the membrane will be negative inside. But if it is only permeable to sodium, it would be positive inside. You can begin to see how cells control their membrane potential(changes in membrane potential = signals) by havinggated ion channels.Vm when several ions are permeableWhat if your membrane is permeable to different ions, and to different degrees? What would the membrane potential of the whole cell be?(General mammalian values: -90 = Ek, +70 = Ena) The membrane potential depends on 2things – relative permeability of each ion(the more permeable an ion is, the moreinfluence it will have) and the relativeconcentrations of each ion across themembrane. This is seen in the Goldman-Hodgkin-Katz equation, where P is thepermeability constant. Notice that Chlorideis in over out(opposite of others) - you haveto flip it because it is an anion while theothers are cations.Key Rules-If the permeability for a particular ion increases, the membrane potential will change, tending to move toward the equilibrium potential for that ion. In other words, if the permeability of a particular ion increases, then it will have a more important effect on the Vm. -If the permeability of a particular ion is very low, approaching 0, then that term just drops out and becomes 0 and doesn’t contribute to membrane potential.Ion Leakage and Na/K pumpsThe membrane of a cell is pictured above. It has two open ion channels, one for K and one for Na. The concentrations are shown. A typical cell will have both open Na and open K channels. So what is the membrane potential going to be? If the actual Vm = -70(inside is negative), neither ion is at equilibrium. -The potential at which K’s outward chemical diffusion and inward electrical diffusion is equal and opposite is -90, not -70. At -70, the concentration gradient driving K out remains the same, but the electrical gradient is weaker. Outward movement becomes greater than inward movement, and so there is net outward movement of potassium. -What about for Na? The membrane would have to be +60 inside, in order for the inward movement of Na down its concentration gradient to be balanced by an outward electrical gradient. So there is a huge net inward current for sodium.If you are not at equilibrium potential, then there is a force due to the difference between membrane potential and the equilibrium potential for the ion. This force (Vm-Eion) is the driving force making the ion move. For Na, the driving force is -70 MINUS a +60. = -130. A negative driving force means the resulting cation movement will be inwards. -130mV is the force driving a strong inward movement of Na into the cell. For K, it would be -70+90 = +20, sowe have outward movement of the cation. If anion, it’s the opposite. So there is a force of 130 pushing Na inwards, and one of 20 pushing K outwards meaning ions are typically leaking in andout all the time. The cell has a finite small volume however, so to combat this, it has a pump that moves sodium back out and gets K back in. The Na/K pump plays a vital role in maintaining distribution of ions/concentration gradient that makes this possible. More sodium coming in and K getting out stimulates the pump to work faster as long as there is ATP. *Bonus Hererra Tangent: Neurons, which use the leakage of ions through channels to generate signals, have a lot of Na/K pumps. Babies have active neurons that are growing and going under rapid cell division, and it is important they get enough energy to power the metabolism of their