The Effect Of Calcium Channels On The Brain

_ The resting neuron is 4 to 5 times more permeable to K+ then to Na+ because of the leakage channels._

The most frequent inflammatory disease of the central nervous system (CNS) impacts the lives of two and half million people in the world, Multiple Sclerosis (MS) (Schattling, 2013). Growing up, this disease has personally affected my family, and seeing a first hand account of the burden and turmoil that this disease causes for all of its patients it is critical to understand how this disease degenerates neurons and axons. The key players in this process are nervous system ion channels that regulate the influx and efflux of sodium and calcium, whether through exchangers or voltage-gated channels. There are normal molecular settings in neurons and there are MS molecular settings; the two are very different and progressively become further

The cell membrane proteins pump what is called sodium ions out of the neuron and then will pump potassium ions into the neuron. An active transport mechanism and leaking back forth of both sodium ion and potassium ion will produce a negative charge on the inside of the neuron’s cell membrane.

It plays a significant role in many neurological functions, including brain plasticity (4), learning and memory (5), and induction of pain (6). Poor or excess release of glutamate can cause serious neurodevelopmental and neurodegenerative disorders such as autism (7-9), epilepsy (7, 10-13), schizophrenia (14), Alzheimer’s disease (14-17) and Parkinson’s disease (18, 19). Physiologically, glutamate is released from pre-synaptic vesicles into neuronal synapses in response to action potential. The concentration of glutamate within the vesicles is reported to be ~100 mmol/L (20). The action potential firing mechanism primarily involves the movement of cations (Ca2+, Na+ and K+) across the neuronal membrane. Two voltage-gated ion-channels located in the axon permit active transport of K+ and Na+, into and out of the cells (20). This ion exchange creates a potential difference of -70 mV (resting potential) through the neuronal membrane. Sudden depolarisation or action potential occurs when potential drops, allowing Na+ to flood into the cells. Action potential is terminated to restore the resting potential of the membrane. Ca2+ channels open to allow the transport of Ca2+ (2). This ultimately causes glutamate to be released from its vesicle into the area between presynaptic membrane and postsynaptic membrane of the subsequent neuron. Through this electrochemical signal

Cells respond to stimuli from the environment by enabling the passage of ions across the plasma membrane, a process that results in the propagation of an electrical signal. Ion channels are the key players of this process, the membranes of excitable cells are studded with a myriad of these integral membrane proteins, which transduce chemical and electrical stimuli into currents of charged chemical species (Hille, 2001). Owing to their pivotal role in cell physiology, a large number of genes encode for ion

Increasing extracellular K+ reduces the net diffusion of K+ out of the neuron through the K+ leak channels because the membrane is permeable to K+ ions. Therefore, the K+ ions will diffuse down its concentration gradient from a region of higher concentration to a region of lower concentration.

The Na+ and K+ potentials are the membrane

From the Module 5: Ion channels part 2, an action potential is generated by voltage gated sodium and potassium channels and happens when the intercellular sodium influx is greater than the intercellular potassium influx. When a cell encounters a stimulus or an injection, the cell depolarizes. Sodium’s equilibrium potential is around +40-50mV, causing the electrochemical force to drive the cell as close to its desired potential as possible. As more of the cell depolarizes more sodium’s equibrium potential becomes smaller creating a larger sodium current. Sodium would remain at its equilibrium potential if not for the opposing forces such as sodium channel inactivation and potassium channel activation. Different from deactivation, sodium channels have a

These channels function as voltage-sensors that initiate depolarization-induced Ca2+ release from the SR as well as voltage-gated Ca2+ channels. The channelopathy involved with calcium ion channels is homologous to sodium channels and can cause hypokalemic periodic paralysis through similar fashion of gating pore current and, in rare cases, malignant hyperthermia due to changes in Ca2+ currents. The mutation that causes the channelopathy causes ions to travel through an S4 segment of the voltage-sensor domain similar to the sodium ion channel. This gating pore is voltage-dependent and active at hyperpolarized potentials. It is also susceptible to paradoxical depolarization in low K¬+¬ concentrations and causes K+-sensitive periodic

In multi-cellular organisms, cells are characterized by energetically favorable gradient moving potassium from the intracellular to the extracellular environment. Inwardly rectifying potassium-selective (Kir), channels encoded by the KCNJ gene family are constitutively active and favor the influx of potassium more readily than its efflux from the cells, thereby maintaining potassium homeostasis. Kir channels are also known as IRK or KCNJ channels. Fifteen mammalian KCNJ gene products have been described which result in seven distinct Kir channels (Hibino et al., 2010; Sharman et al., 2011). These channels are located within the plasma membrane of most cell types, where they regulate membrane potential and potassium homeostasis (Table 1)

When the channels open (in response to depolarization in transmembrane voltage[b]), they allow an inward flow of sodium ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential. This then causes more channels to open, producing a greater electric current across the cell membrane, and so on. The process proceeds explosively until all of the available ion channels are open, resulting in a large upswing in the membrane potential. The rapid influx of sodium ions causes the polarity of the plasma membrane to reverse, and the ion channels then rapidly inactivate. As the sodium channels close, sodium ions can no longer enter the neuron, and then they are actively transported back out of the plasma membrane. Potassium channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, called the afterhyperpolarization or refractory period, due to additional potassium currents. This mechanism prevents an action potential from traveling back the way it just

However, an experiment performed by Hodgkin and Huxley looked at the role of Na+ during action potentials using the giant squid axon. While this experiment involved membrane voltage during action potentials and our experiment looks at the membrane at rest, it still shows that the membrane can be permeable to Na+ (Hodgkin and Huxley 1952). However, through the results of our experiment it cannot be empirically concluded which ions, besides potassium, played a role in changing membrane potential.

Each subunit has a long extracellular N-terminus, followed by 4 transmembrane helices (M1–M4), which are separated by loops. The extracellular N-terminal domain comprises the agonist binding site [38, 49]. In the pentameric structure the channel pore is formed by a bundle of five M2 helices, each contributed by one the subunits. Residues within or in the vicinity of M2 are the basis of ion selectivity. The presence of negatively charged residues such as glutamate/aspartate near the cytosolic and extracellular transmembrane boundaries of M2 confer selectivity to cations whereas the positively charged/polar or neutral residues are those that confer anion

The action potential arrives at the axon terminal. Calcium channels open allowing calcium ions to enter the axon terminal. Acetylcholine is released into the synaptic cleft and calcium ions are pumped out of the axon terminal. Acetylcholine binds to receptor sites on the motor end plate. An action potential is generated which propagates and travels down t-tubulues. The action potential causes the release of calcium ions. Calcium ions trigger a contraction of the muscle cell.

Erwin Neher and Bert Sakmann in 1991: discoveries concerning the function of single ion channels in cells