Essay Sample on Anesthetics: Essential Tool for Pain-Free Surgery

Introduction

Anesthesia refers to any medical treatment that is used to prevent patients from feeling pain during surgery. For years now, anesthesia has allowed people to undergo procedures that enable them to lead longer and healthier lives. Anesthetics are used to produce anesthesia. Different anesthetics have different effects. They are also delivered using various means depending on the kind of pain relief required. While general anesthetics affect the whole body and makes the patient unconscious, local anesthetics block pain in a specific part of the body. It is believed that anesthetics work by targeting proteins in the membranes of the nerve cells. This paper seeks to discuss the role of potassium channels in the action of ketamine.

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Ketamine is a general anesthetic that has traditionally been believed to work by antagonizing N-methyl-D-aspartate (NMDA) receptors (Voss, Karalus, Englund, & Sleigh, 2018). However, the belief has been challenged over the years. For instance, research has shown that both NMDA antagonist MK-8012 and NR2A NMDA-receptor subunit have no anesthestic effect in mice (Voss, Karalus, Englund, & Sleigh, 2018). This notwithstanding, NMDA receptors should not wholly be disregarded. Instead, there is a need for research into additional targets that can explain the functioning of ketamine as an anesthetic. Just like the majority of general anesthetics, ketamine acts at several levels of the nervous system. Therefore, anyone of them could be responsible for ketamine anesthesia (Voss, Karalus, Englund, & Sleigh, 2018).

The potassium and hyperpolarization-activated cyclic nucleotide-gated channels have been identified as prime candidates (Voss, Karalus, Englund, & Sleigh, 2018). By stereoselectively blocking hyperpolarization-activated cyclic nucleotide-gated-1 channels, ketamine leads to membrane hyperpolarization (Voss, Karalus, Englund, & Sleigh, 2018). However, the action of ketamine on the potassium channels is not completely understood. Though ketamine causes blockade of potassium channels, it occurs at clinically irrelevant concentrations. The two-pore potassium channels, popularly known as leak channels, therefore, present a more probable target for ketamine. The two-pore potassium channels control the resting membrane potential and are also targeted by other anesthetics including anesthetic gases and volatiles (Voss, Karalus, Englund, & Sleigh, 2018). However, the effect of ketamine on the two-pore potassium channels is not well understood.

Various studies have been carried out in an attempt to understand how ketamine acts on potassium and hyperpolarization-activated cyclic nucleotide-gated channels. In one such study, an in vitro model was used. The cortical slice no-magnesium seizure-like event model was used in the study. It was hypothesized that any pharmacologic alteration of the potassium channels would affect the ketamine inhibition of seizure-like activity (Voss, Karalus, Englund, & Sleigh, 2018). This would be a confirmation of the role of potassium leak channels on the mode of action of ketamine. Coronal brain slices obtained from wild mice aged between two and six months were used. When perfused with no-magnesium artificial cerebral spinal fluid, all the slices generated spontaneous seizure-like activity. No difference was observed in baseline seizure-like activity for spices prepared in carbonate-buffered artificial cerebrospinal fluid and HEPES (Voss, Karalus, Englund, & Sleigh, 2018). The study focused on the frequency of the seizure-like activity since anesthetic drugs modulate the frequency. The ability of an anesthetic to reduce the frequency of seizure-like activity in the cortical slice is directly proportional to its potency (Voss, Karalus, Englund, & Sleigh, 2018). Just as observed in previous studies, ketamine led to a reduction in seizure-like activity in all the slices.

On the other hand, exposure to the hyperpolarization-activated cyclic nucleotide-gated channel antagonist ZD7288 did not cause any change in the seizure-like activity. However, it was noted that a higher concentration of ZD7288 led to a significant reduction in the frequency of seizure-like activity (Voss, Karalus, Englund, & Sleigh, 2018). Ketamine inhibition of the seizure-like activity was not altered by ZD7288. High levels of cesium chloride were found to affect both potassium and hyperpolarization-activated cyclic nucleotide-gated channels. Since ZD7288 does not affect the activity of ketamine, the study concluded that reduction in the inhibition function of ketamine by cesium was as a result of potassium channel effect, particularly the blockade of the leak channel (Voss, Karalus, Englund, & Sleigh, 2018). The researchers postulated that if potassium leak channels are opened by ketamine, increasing potassium leak currents would lead to an increase in the ketamine inhibition of seizure-like activity. Reduction of artificial cerebrospinal fluid potassium concentrations led to a significant increase in the ketamine inhibition of seizure-like activity. Therefore, enhancement of conductance of potassium leaks came across as an essential function of ketamine.

Conclusion

This study concluded that hyperpolarization-activated cyclic nucleotide-gated channels play a role in the anesthetic activity of ketamine. However, the study pointed to the likelihood of other mechanisms. Since ZD7288 did not affect seizure-like activity, it was concluded that the effect of cesium chloride was not an action of the hyperpolarization-activated cyclic nucleotide-gated channel. The agonist action of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) explains the increase in seizure-like activity in response to cesium (Voss, Karalus, Englund, & Sleigh, 2018). However, various findings of the study discount this explanation. The blocking effect of barium on the anesthetic was interpreted as an antagonistic action at the same receptor. Though the study strongly pointed to the potassium channels in the action of ketamine, the possibility of a physiologic antagonistic effect cannot be ruled out. Genetic manipulations, pharmacologic blockers, as well as electrophysiologic blockers, can offer more explanation onto whether ketamine activates one or more leak channels (Voss, Karalus, Englund, & Sleigh, 2018).

References

Voss, L. J., Karalus, S., Englund, V., & Sleigh, J. W. (2018). Ketamine Action in the In Vitro Cortical Slice Is Mitigated by Potassium Channel Blockade. Anesthesiology, 128(6), 1167-1174.