Contribution of the LEV-8 Subunit to the Kinetics of Activation and Desensitization of Levamisole-Sensitive Nematode Muscle Nicotinic Receptors

HERNANDO GUILLERMINA; RAYES DIEGO; BOUZAT CECILIA

Huerta Grande, Córdoba

Congreso; Second Joint Meeting of the Argentine Society for Neuroscience (SAN) and the Argentine Workshop in Neurosciences (TAN).; 2010

Sociedad Argentina de Investigación en Neurociencias (SAN)

The levamisole-sensitive nicotinic acetylcholine receptor (L-AChR) is a pentameric protein involved in neuro-muscle transmission of C. elegans. These receptors appear to be composed of three essential (UNC-63, UNC-38, and UNC-29) and two accessory subunits (LEV-1 and LEV-8). We explored the contribution of the alpha-type LEV-8 subunit to the kinetics of activation and desensitization of L-AChRs from C. elegans muscle cultured cells.Single-channel activity of L-AChRs can be detected from LEV-8 null mutant strain, confirming that LEV-8 is not an essential subunit. Channel conductance is similar to that of wild-type L-AChRs (~36 pS). In contrast, in the null mutant the duration of the slowest open component is about 3-fold more prolonged. In addition, a dramatic difference between recordings from LEV-8 null mutant and wild-type muscle cells is a time-dependent reduction in the frequency of opening events, suggesting enhanced desensitization. ACh-elicited macroscopic currents show that the decay time constant is ~4-fold reduced in the mutant compared to wild-type L-AChRs, therefore confirming faster desensitization. ). Thus, the properties of L-AChRs-mediated responses in muscle cells can be substantially changed whether or not accessory LEV-8 subunit is incorporated into the receptor.