It was already stated, based on experimental evidence, that ”the membrane permeability to the ions has nothing to do with the potential generation and the ions adsorption on the membrane surface generates the membrane potential”, for a review see [74]. The idea itself is nonsense: in a balanced state, no ion transport happens, so even without permeability, the balanced state persists; the resting potential has nothing to do with either ions’ mobility or permeability nor with ion absorption [75]. Furthermore, there is no idea in GHK about whether the ’setpoint’ (why that specific concentration or potential difference) is present and why the same potential is reset after rough perturbations such as issuing an AP or replicating a cell. The causality is reversed: the potential is a static concept which is set electrically, and the two gradients form the experienced concentrations and potentials from the available solvent molecules. For the time course of forming the gradients, mobility and permeability play a role, but not in determining the concentrations or the resting potential.
In our clear physical picture, the thermodynamic forces on the one side and on the other side of the membrane are summed. They counterbalance each other; furthermore, jointly the effect of the neuronal condenser, see Fig. 1.5. As we emphasized, the concentration gradients are ion-specific. Furthermore, as we discussed in connection with Eq.(2.20), the Nernst equation comprises a per-ion indefinite constant (a potential difference). To calculate a linear combination of terms comprising an arbitrary constant is nonsense, and so is adding absolute concentrations on the different sides of the membrane, or changing the base of the logarithm used in a calculation to match the experimental value. It is not more than number magic. The potential is described by coupled equations as discussed in connection with Eq. (1.2).
The ions do not fit into the GHK picture. One of the reasons why GHK cannot be good is that is omitted. Biologically, it is hard to believe that does not participate in the game of life (especially since biology sees the need for pumps). Physically, one concentration alone on one side of the membrane cannot keep balance; as the different ion exchange processes, Table 3.1 and Fig. 1.5 show. When adding a new ion to the solution, the sum concentration increases, and so the electrical force increases, forcing the previous elements to find new concentrations on both sides. The appearance of a new chemical element indirectly changes the concentrations of the others (a good example is the role of the negligible amount of ).
In the light of our findings, we must reconsider a few key conceptions. We derived (see Eq.(2.71)) that the gap voltage depends on the thickness of the membrane and the overall concentration. Furthermore, we demonstrated that the gap voltage is equivalent to the resting potential (correctly: potential difference) and is independent of ion mobility or ion composition in the solution. Derived values, such as the Goldman-Hodgkin-Katz potential, should be rethought. The idea is nonsense: in a balanced state, no ion transport happens, so even without permeability, the balanced state persists; as experiments proved, the resting potential has nothing to do with either ions’ mobility or permeability nor with ion absorption [75]. The causality is reversed: the potential is a static notion and is set electrically, and the two gradients form the experienced concentrations from the available solvent molecules. For the time course of forming the gradients and maintaining the balance, mobility and permeability play a role but not in determining the concentrations or the resting potential.
The ions do not fit into the GHK picture. However (see our Table 3.1), it provides a thermodynamic contribution in the same order of magnitude as the charge separation by the membrane. If we add the potential due to , we arrive at the correct result that the total balance of the thermodynamic contributions equals zero, that is, the resting potential is zero. The electrical potential contribution is an additional term, resulting in the resting potential.
When adding a new ion to the solution, the sum concentration increases, and so the electrical force increases, forcing the previous elements to find new concentrations on both sides. The appearance of a new chemical element indirectly changes the concentrations of the others (a good example is the role of the negligible amount of ). No linear summing or similar assumptions can be made. The potential is described by coupled equations as discussed in connection with Eq.(1.2). As we discussed in connection with Eq.(2.20), the integral form of the Nernst equation implies an undetermined additive constant. To calculate a linear combination of terms comprising an arbitrary constant is nonsense, and so is changing the base of the logarithm used in a calculation to match the experimental value.