Nicotinic Acetylcholine Receptor Gene Expression Is Altered in Burn Patients

• Published in: Anesthesia and analgesia Vol. 110; no. 5; pp. 1355 - 1359
• Main Authors: Osta, Walid A., El-Osta, Mohamed A., Pezhman, Eric A., Raad, Robert A., Ferguson, Kris, Mckelvey, George M., Marsh, Harold M., White, Michael, Perov, Samuel
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01-05-2010; Lippincott Williams & Wilkins
• Subjects: Adult; alpha7 Nicotinic Acetylcholine Receptor; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Burns - genetics; Burns - metabolism; DNA - biosynthesis; DNA - isolation & purification; DNA Primers; Female; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Humans; Male; Medical sciences; Mouth Mucosa - metabolism; Receptors, Nicotinic - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - isolation & purification; Up-Regulation; Burn; Human; Neurotransmitter; Anesthesia; Acetylcholine; Gene expression
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1213/ANE.0b013e3181d41512

Burn patients have been observed to be more susceptible to the hyperkalemic effect of the depolarizing muscle relaxant succinylcholine. Changes in nicotinic acetylcholine receptor (nAChR) subunit composition may alter electrophysiologic, pharmacologic, and metabolic characteristics of the receptor inducing hyperkalemia on exposure to succinylcholine. No studies have been performed that show the upregulation and/or alteration of nAChR subunit composition in human burn patients. The scarcity of studies performed on humans with burn injury is mainly attributable to the technical and ethical difficulties in obtaining muscle biopsies at different time frames of illness in these acutely injured patients. nAChRs are expressed in oral keratinocytes and are upregulated or altered in smokers. However, no studies have addressed the expression of nAChRs in the oral mucosa of burn patients.
Buccal mucosal scrapings were collected from 9 burn patients and 6 control nonburn surgical intensive care unit patients. For burn and control patients, tissues were collected upon presentation (time: 0 hour) and at time points 12, 24, and 48 hours, 1 week, and 2 weeks. Gene expression of the nAChR subunits alpha1, alpha7, gamma, and epsilon were performed using real-time reverse transcriptase polymerase chain reaction.
alpha7 and gamma nAChR genes were significantly upregulated in burn patients, whereas alpha1 and epsilon nAChR genes were minimally affected, showing no significant changes over time.
Over the 2 weeks of measurement, an upregulation of the alpha7 and gamma genes occurred in both burn and control patients; however, the proportion of alpha7 and gamma subunit increases was significantly higher in burn patients than in control surgical intensive care unit patients. The relationship between the thermal injury and the observed alteration in gene expression suggests a possible cause/effect relationship. This effect was observed at a site not affected by the burn injury and in nonmuscle tissues, thus emphasizing the systemic nature of the effect caused by the thermal injury. Because gene expression is the basis of protein production, the upregulation of alpha7 and gamma genes might translate into more alpha7 and gamma protein subunits. These proteins can also combine with each other or with other types of subunits (alpha1, beta, epsilon . . .) to form nAChRs with altered electrophysiologic characteristics leading to the observed abnormal clinical outcomes.
Thermal injury may infer a systemic effect because upregulation/alteration of nAChRs occurs in nonmuscle tissues distant from the site of injury. The effect of thermal injury on nAChR gene subunits can be studied using a minimally invasive method (buccal mucosal scraping) and a highly sensitive technology (real-time reverse transcriptase polymerase chain reaction) obviating the need for more invasive methods.