Where in the nervous system would you find voltage gated calcium channels and what is their role?

The voltage-gated calcium channels are a group of proteins located in the central nervous system and the peripheral tissue. These ions are present in the membranes of excitable parts and cells, such as muscles. They are responsible for the regulation of many processes of the cell, owing to their electrogenic features. They release depolarization-induced entry of calcium into the neurons, muscles, and any other excitable cell. The calcium entry also occurs in non-excitable cells as well, due to the depolarization that originates from the voltage-gated calcium channels. The calcium channels further mediate functions such as muscle contraction, the release of neurotransmitters, as well as hormones by neurons. Also, the calcium channels control the transcription of genes.

Why would inhibiting the VGCCs result in skeletal muscle weakness?

Every muscle in the human body requires energy to function normally, and skeletal muscles are not an exception. The energy so needed comes from the process of metabolism, whose occurrence and control revolves around the calcium ions. As such, the muscles will require the calcium ions to enable it to gain energy through metabolism. For the ions to get to the muscles, they need to go through the voltage-gated calcium channels. As such, the inhibition of the voltage-gated calcium ions would mean that the calcium ions will not reach the muscles. Their absence will lead to their deficiency, which in turn will lead to lower metabolism and consequently lower energy production. With less energy, then, skeletal muscles weakness is inevitable. (Mda.org, 2018)

One of the symptoms of LEMS is “autonomic disturbance”. Using your knowledge of the autonomic system and the transmitters that are released, would you expect to see disturbances in both the sympathetic and parasympathetic branches? Make sure that you justify your response.

The autonomic nervous system comprises two major branches, namely the sympathetic branch and the parasympathetic branch. This autonomic nervous system regulates bodily functions such as digestion, heartbeat rate, urination, as well as sexual functionality. The two branches have different influences on the internal organs. If one of the branches initiates a certain physiological process, the other branch will inhibit it. Both of the divisions release acetylcholine as the neurotransmitter, at the synapse in the ganglion. However, the sympathetic system has postganglionic neurons which release norepinephrine as the neurotransmitter.

The autonomic disturbance has signs such as dizziness, fainting, inability to change the rate of the heartbeat with the change in exercise, as well as failing to exercise for a long time due to inherent muscle fatigue. In some cases, symptoms such as digestive problems may arise. These problems include constipation, loss of appetite, and bloating. A patient with autonomic disturbance will exhibit other signs such as difficulties emptying the urinary bladder, erectile dysfunction in men, as well as vaginal dryness in women. All these physiological processes have their regulations based in the neurotransmitters in both the sympathetic and parasympathetic divisions of the central nervous system. For this reason, an autonomic disturbance would lead to disturbances in both divisions. (Emedicine.medscape.com, 2018)

The first line therapy for LEMS is treatment with a voltage gated K+ channel blocker such as amifampridine (3,4-diaminopyridine). Why do you think that this would be effective? In your answer include where you would find voltage gated K+ channels, what role they play in the nervous system and how their inhibition would improve symptoms of LEMS.

In treating the LEMS disease, it is advisable to use the voltage-gated potassium channel blocker. Voltage-gated potassium channel plays an essential role in taking back the depolarized cell to the resting state. Since LEMS arise due to depolarization of the cell for calcium entry, it is advisable to use the voltage-gated potassium blocker to neutralize the whole effect. When using the calcium-activated potassium channel, it opens to respond to the presence of calcium ions and other molecules around the depolarized cell. The potassium channels are present in the central nervous system and the peripheral nervous system.

The role they play depends on the type of channel. For instance, the inwardly rectifying potassium channel passes positive charge inwardly through the membrane into the cell. As earlier stated, the role that these channels play about calcium is that they return the depolarized cell to its resting position. Therefore, inhibiting the channels would mean that the depolarized cells remain in the same state, and therefore the treatment of the symptoms will be slower. (Rarediseases.orG, 2018)

If a patient suffered from a disease where only the voltage gated calcium channels on muscle cells were targeted by antibodies, which type of muscle, skeletal or smooth, would be most affected and why?

In case a patient suffered from an illness caused by antibodies that target only the voltage-gated calcium channels on muscle cell, the most affected type of muscle would be the skeletal muscle. As earlier analyzed, the skeletal muscles require the voltage-gated calcium channels to facilitate energy production through metabolism. When the antibodies target the calcium channels, they would treat the channels as pathogens and thus attack them. Doing so would inhibit their functioning, and in the end, the skeletal muscles would feel the greater impact of the disease. It has more of the calcium channels, whose inhibition would have adverse effects.

References of The voltage-gated calcium channels

Emedicine.medscape.com. (2018). Lambert-Eaton Myasthenic Syndrome (LEMS). Retrieved from https://emedicine.medscape.com/article/1170810-overview

Mda.org. (2018). Lambert-Eaton Myasthenic Syndrome (LEMS). Retrieved from https://www.mda.org/disease/lambert-eaton-myasthenic-syndrome

Rarediseases.orG. (2018). Lambert-Eaton Myasthenic Syndrome. Retrieved from https://rarediseases.org/rare-diseases/lambert-eaton-myasthenic-syndrome/