Roles of Potassium, Sodium and Calcium Ions in the Conduction of Messages Down a Neuron

Introduction

 Transmittal of messages down a neuron and between neurons is accomplished through a complex array of electrochemical processes at the molecular level. These processes are governed by positively or negatively charged ions which determine the electrical charge of neurons and trigger the method by which messages are created and travel. In the most simplistic terms, potassium ions (K+) control the resting potential of the neuron which is the -60mV negative charge on the interior of the neural membrane in the absence of stimulus, sodium ions (Na+) control the nerve impulse or Action Potential (AP) which carry messages down a neuron and calcium ions (Ca2+) regulate the release of neurotransmitters into the synapse between neurons ensuring the transmittal of messages from neuron to neuron. The mechanisms by which these ions operate to exert influence on the creation and conduct of messages down a neuron are a set of ion channels that specifically react to K+, Na+ or Ca2+. The ions themselves play a central role in the shift of electrochemical charge in the neuron which determines how an AP is created and how it is transmitted. This analysis will provide an overview of the conduct of messages down a neuron, setting the context for the role of the three ions in question, then treat the specific role of each of K+, Na+ and Ca2+ ions in turn.

Overview of conduction of messages down a neuron

 This overview explains how messages in neurons are created and carried by an electrochemical process in and between neurons. The overview starts from the point at which a nerve impulse, represented by a small electrical current or action potential (AP), is or is not fired in the neuron cell body (soma) at the point of the axon hillock (the physical point where the soma attaches to the axon). The overview next explains how that current travels down the neuronal axon, describing how it is transmitted to another neuron, which continues the cycle of the conduct of messages through neurons. The specific contributions of potassium, sodium and calcium ions will be discussed in detail in following sections of this paper.

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 The initiation of an AP, which is a current generated by a short but pronounced change in neuronal polarisation (Breedlove, Watson & Rosenzweig, 2010), can be viewed as the start of the messaging process. In short, the neuron is stimulated by either excitatory or inhibitory synapses where another neuron has affected the membranes of the dendrites or soma of the neuron. These stimuli produce either an excitatory postsynaptic potential (EPSP) where the postsynaptic neuron is depolarised, becoming positively charged, or producing an inhibitory postsynaptic potential (IPSP) where the postsynaptic neuron is hyperpolarised, becoming more negatively charged. Whether an EPSP or an IPSP is produced is determined by the charge instigated by the neurotransmitter once it binds to receptors in the postsynaptic neuron. The postsynaptic neuron then goes through a process of summation, balancing the EPSPs and IPSPs to determine whether the depolarisation is sufficient to surpass the threshold of excitation, approximately +40mV, which shifts the neuron from its resting potential, the negative electrical charge of the neuron in the absence of EPSPs or IPSPs, to create the AP which is marked by a brief reversal of charge to the positive (Breedlove et al, 2010).

 The size of all APs once fired are the same and their role in the message transmitted down the axon is dependent on their frequency and patterns not the size of the stimulus that created them (Purves, Augustine, Fitzpatrick, Hall, McNamara & White, 2014). To move down the axon, APs are created at contiguous points along the axon as the depolarised segment of the axon depolarises the point next to it due to local current flow. APs move down the axon by regenerating as they reach each node of Ranvier, the gaps between myelin sheaths covering the axon. This is called saltatory conduction. When moving down the axon under the myelin sheath, the AP degrades due to the sheath’s inhibitory effect on the movement of K+ ions out of the axonal membrane, maintaining the depolarisation (explained in detail below). At successive nodes of Ranvier, the AP is regenerated since the absence of the sheath at the node no longer inhibits ion activity and Na+ ions move across the axonal membrane regenerating the AP (Breedlove et al, 2010).

It is important to note that APs move down the axon and not in the opposite direction up the soma or through the dendrites for two reasons. First, for a short time after the triggering of APs the axonal membrane becomes insensitive to stimulus and goes into a refractory phase, preventing more APs from being generated at that point in the axon. In addition, the soma and dendrites do not possess sufficient voltage-gated Na+ channels which are necessary for sodium ions to provide the depolarisation required for an AP to fire (Breedlove et al, 2010).

 Once the message contained in the AP reaches the presynaptic axon terminal, the AP plays a critical role in passing on the message to another neuron. When the AP reaches the axon terminal, also called the axon button, it stimulates exocytosis whereby the neurotransmitters contained in the presynaptic vesicles in the axonal button are released into the synaptic cleft between the presynaptic axon button and the postsynaptic membrane of another neuron. This occurs when the vesicles bind with the presynaptic membrane of the axon button and are opened through widening of a fusion pore in the membrane through which the neurotransmitters are released (Breedlove et al, 2010). The critical role of Ca2+ in this process is described below.

 The next step in the process is for neurotransmitters to bind with their specific receptors in the postsynaptic membrane, usually at the dendrite of the receptor neuron. The binding opens ion channels that allow ions to move into the postsynaptic neuron. The opening and closing of multiple ion channels of varying positive or negative charge determine the excitatory or inhibitory nature of the charge in the postsynaptic neuron. This creates the EPSPs or IPSPs which, as described above, summate as they travel toward the axon, through the soma and axon hillock and either pass the excitation threshold to fire an AP or not, beginning the cycle once again (Purves et al, 2014).

 The synaptic processes above which rely on neurotransmitters to make chemically based connections with adjacent neurons is but one of two types of synapses by which messages are transmitted between neurons, albeit the most common. The other is electrically based and occurs when the synaptic cleft between neurons is smaller than in the chemically based processes. In these electrical synapses, or gap junctions, the pores in the membranes align so that current passes directly from one neuron to the other. It is faster as it does not rely on chemical activity of neurotransmitter release and postsynaptic binding (Bennet, 2000; Gibson, Beierlein & Connors, 1999; Landisman & Connors, 2005). Potassium ions also play a key role in gap junctions as will be described below.

The specific role of potassium ions (K+)

 

 The principal role of potassium ions is in regulating the resting potential of the neuron. The resting potential is the electrical charge inside the neuron in the absence of any EPSP or IPSP stimulus. At resting potentialthe charge inside the neuron is approximately -60mV and this negative charge is in contrast to the more positive charge outside the neuron. The resting potential is maintained by large negatively charged molecules that remain inside the cell and the movement of K+ ions through open channels or pores in the neuronal membrane which allow only K+ ions to move freely in and out of the neuron (Breedlove et al, 2010). This preference for the free flow of potassium ions is called selective permeability to potassium.

Two forces operate to determine how much of the K+ ions pass through the channels. The first is electrostatic pressure. As the intracellular space is negatively charged, the positive K+ ions are attracted to the negative charge and rush in through the open channels. Consequently, more K+ ions are present inside the neuronal membrane. Conversely, when there are too many positive ions they will repel each other, sending K+ ions outside of the cell. Potassium ions also are affected by diffusion which seeks to equalise the concentration gradient of ions on the inside and outside of the neuronal membrane. When there are more K+ ions inside the cell than in the extracellular space, K+ ions will flow out of the neuron through K+ channels. When the balance of K+ ions exiting and entering the neuron due to these two forces reaches equilibrium the resting potential is reached and the electrochemical charge inside the neuron is roughly -60mV (Purves et al, 2014).

 Notwithstanding the function of the open K+ channels and the forces of diffusion and electrostatic pressure on K+ ions, the resting potential can be affected by leakage into the neuron of positively charged sodium Na+ ions drawn to the negatively charged cell interior by electrostatic pressure. To correct for this disturbance in the resting potential, a specialised channel through the membrane called the sodium-potassium pump comes into play. Again, K+ ions play a critical role. The pump ejects Na+ ions from the cell interior and attracts K+ ions into the neuron in a 3:2 ratio, thus reducing the number of positive ions inside the neuron, maintaining the negative charge inside the cell and preserving the resting potential (Purves et al, 2014).

In the first instance the pump is open to the cell interior and has affinity for Na+ ions which enter the pore and bind with proteins in the pump. This causes phosphorylation which turns the proteins in the pump into a substrate for the high energy ATP molecule which powers the action of the pump. With this energy the pump closes to the interior of the neuron and opens to the extracellular space. It loses its affinity for the sodium ions, releasing them but now has affinity for K+ ions and attracts K+. They bind with the pump’s proteins. This triggers dephosphorylation, opening the channel to the intracellular space where the K+ ions are released due to the loss of affinity for potassium (Breedlove et al, 2010). Potassium ions are therefore the central regulator in maintaining the neuron’s resting potential and it is the depolarisation from the resting potential that creates the APs which are the messages carried down the neuronal axon.

Another role of K+ ions is in the transmittal of current from one neuron to another in gap junctions. Studies have shown that potassium ions promote synchrony, assisting in membrane alignment for electrical synapses (Pfeuty, Mato, Golomb & Hansel, 2003) and more generally play a role in promoting electrical coupling in neuron cells (Massobrio, Giachello, Ghirardi & Martinola, 2013).

 

The specific role of sodium ions (Na+)

 

 In contrast to the passive role in maintaining the resting potential described above, Na+ ions play a central role in the creation of APs which constitute the messages passed along neurons. Early work by Hodgkin and Katz (1949) discovered that APs were created by Na+ ions moving into neurons through the cellular membrane. The principal mechanism by which sodium ions play this role is the voltage-gated Na+ channel. These channels which are normally closed respond to the positive current as the charge in the cell moves towards the threshold rate of +40mV by opening to allow more Na+ ions into the neuron. This increases the positive charge opening more voltage-gated Na+ channels assisting in spiking the charge over the excitation threshold where the AP is created (Breedlove et al, 2010; Purves et al, 2014). At the creation of the AP, sodium equilibrium is reached, the voltage-gated Na+ channels close and K+ ions resume their role restoring resting potential in the neuron through both open K+ channels and voltage-gated K+ channels which open as the charge returns to a negative state. This blocking of Na+ channels and opening of multiple K+ channels can act to temporarily hyperpolarise the neuron at a negative charge below resting potential. This effect is known as afterpotential which is then corrected by the forces of diffusion and electrostatic pressure to restore resting potential (Breedlove et al, 2010).

 An important role of the Na+ voltage-gated channel is its behaviour after closing. Once closed the channel shuts down for a short time, going into a refractory phase. This assists in directing APs down the axon since an AP would fire in adjacent areas where the channels are operative and not move back up the axon.

Two types of Na+ ions play a role in the AP process. Transient sodium (INa.t)acts swiftly to activate then deactivate and is found in neurons in large concentrations (Shepherd, 2003). These characteristics provide a good fit for the very speedy processes surrounding AP creation which usually occur within milliseconds. Persistent sodium (INa.p) does not inactivate as does (INa.t), is smaller in amplitude but also is activated by depolarisation; consequently it can play a role in pushing the charge over the excitation threshold but sustaining its charge (Shepherd, 2003). This can be useful in creating AP patterns that are required for repetitive neuron activity since a cycle is created between the sustained charge, K+ dependent repolarisation and subsequent re-establishment of the AP without delay (Llinás, 1988; Ogata & Ohishi, 2002; Shepherd, 2003).

The specific role of calcium ions (Ca2+)

 

 The key role played by calcium ions in the transmittal of messages in neurons is as the primary facilitator in the release of neurotransmitters into the synapse, allowing AP messages to be passed to other neurons. When the AP reaches the presynaptic axon button the charge activates voltage-gated Ca2+ channels drawing Ca2+ ions into the axon button. The Ca2+ ions then react with the proteins in the fusion pores in the cell membrane to which the synaptic vesicles containing the neurotransmitters have docked. The fusion pores open, widening an opening in the vesicle allowing the neurotransmitter to leave, entering the synaptic cleft between neurons (Breedlove et al, 2010; Purves et al, 2014). Not only are Ca2+ ions central to the functional aspects of neurotransmitter release, they are a determining factor in the amount of neurotransmitters released as well. Studies have shown that the amount of neurotransmitters released varies directly with the concentration of calcium ions in extracellular fluid (Katz & Miledi, 1971).

 Though neurotransmitter release is the principal role of Ca2+ ions in moving messages between neurons, they also play other more minor roles. Their positive charge assists in bringing the neuronal charge to excitation threshold contributing to creation of APs, though this role is secondary to the Na+ and K+ roles in this process described above. In addition, calcium ions entering through high voltage-gated Ca2+ channels contribute to creation of some specific K+ currents which influence the pattern of APs and thus the content of the messages transmitted down the neuron (Sah & Faber, 2002; Shepherd, 2003).

 

Conclusion

The conduction of messages down a neuron is a highly complex electrochemical process at the molecular level largely controlled by proteins and ions. It is clear from the body of research in the field that the central role of potassium ions (K+) is to control the resting potential of the neuron which serves as the starting condition for eventual stimulation and creation of neuronal messages carried by APs. The pivotal role of sodium ions (Na+) is to trigger and control the AP as they carry messages down a neuron and the key contribution of calcium ions (Ca2+) is to regulate the release of neurotransmitters into the synapse between neurons ensuring the transmittal of messages from neuron to neuron. By these specific contributions, these ions enable messages to pass through neurons, the circuits they inhabit and enable the complex functions of brain activity.

References

Bennett, M. V. (2000). Electrical synapses, a personal perspective (or history). Brain Research Reviews, 32(1), 16-28.

Breedlove, S. M., Watson, N. V., & Rosenzweig, M. R. (2010). Biological psychology. Sunderland, MA: Sinauer associates.

Gibson, J. R., Beierlein, M., & Connors, B. W. (1999). Two networks of electrically coupled inhibitory neurons in neocortex. Nature, 402(6757), 75.

Hodgkin, A. L., & Katz, B. (1949). The effect of sodium ions on the electrical activity of the giant axon of the squid. The Journal of physiology, 108(1), 37-77.

Katz, B., & Miledi, R. (1971). The effect of prolonged depolarization on synaptic transfer in the stellate ganglion of the squid. The Journal of physiology, 216(2), 503-512.

Landisman, C. E., & Connors, B. W. (2005). Long-term modulation of electrical synapses in the mammalian thalamus. Science, 310(5755), 1809-1813.

Llinás, R. R. (1988). The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science, 242(4886), 1654-1664.

Massobrio, P., Giachello, C. N., Ghirardi, M., & Martinoia, S. (2013). Selective modulation of chemical and electrical synapses of Helix neuronal networks during in vitro development. BMC neuroscience, 14(1), 22.

Ogata, N., & Ohishi, Y. (2002). Molecular diversity of structure and function of the voltage-gated Na+ channels. The Japanese Journal of Pharmacology, 88(4), 365-377.

Pfeuty, B., Mato, G., Golomb, D., & Hansel, D. (2003). Electrical synapses and synchrony: the role of intrinsic currents. Journal of Neuroscience, 23(15), 6280-6294.

Purves, D., Augustine, G. J., Fitzpatrick, D., Hall, W. C., LaMantia, A. S., McNamara, J. O., & White, L. E. (2014). Neuroscience, 2008. De Boeck, Sinauer, Sunderland, Mass.

Sah, P., & Faber, E. L. (2002). Channels underlying neuronal calcium-activated potassium currents. Progress in neurobiology, 66(5), 345-353.

Shepherd, G. M. (Ed.). (2003). The synaptic organization of the brain. Oxford university press.