Abstract
The nicotinic acetylcholine receptor (nAChR), located in the cell membranes of neurons and muscle cells, mediates the transmission of nerve impulses across cholinergic synapses. The nAChR is also found in the electric organs of electric rays (e.g. Torpedo californica). Cholesterol is a key lipid for maintaining the correct functionality of membrane proteins and has been found to alter the nAChR function. We were thus interested to probe the changes in the functionality of different nAChRs when expressed in cell membranes with modified cholesterol to phospholipid ratios (C/P). In this study, we examined. The effect of increasing the C/P of Xenopus laevis oocytes expressing the muscle-type, Torpedo californica, neuronal a7 or α4β2 nAChRs in the function of the nAChR was studied. Using the two-electrode voltage clamp technique it was found that the neuronal α7 and Torpedo nAChRs are significantly more sensitive to small increases in C/P than the muscle-type nAChR and the neuronal α4β2 nAChR, which is more sensitive than the muscle-type nAChR, but less sensitive than α7 and Torpedo nAChRs. This study clearly illustrates that a physiologically relevant increase in membrane cholesterol concentration alters the neuronal α7 and Torpedo nAChRs functionality whereas the muscle-type nAChR tends to resist this inhibition in function.
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