The N-Aβ fragment enhances α7-nAChR open-dwell time and total burst duration
After analyzing Popen we measured differences in α7*-nAChR single-channel open-dwell times within bursts (Figure 4A). Beginning with homomeric α7-nAChR, open-dwell times within bursts were best fit with two components (C1 and C2; see methods). No significant interaction was observed between receptor subtype and treatment for C1 open-dwell times (Figure 4B; F(7,72) = 1.3; P > 0.05). However, there was a significant interaction for C2 mean open-dwell times across ligand treatment conditions (Figure 4C; F(7,24) = 21.0; P < 0.0001). Specifically, an increase in C2 was observed for homomeric α7-nAChR exposed to N-Aβ fragment alone (P < 0.05) or to ACh + N-Aβ fragment (P < 0.0001) when compared to α7-nAChR exposed to ACh alone. Additionally, the effect in the presence of ACh + N-Aβ fragment was statistically greater compared to treatment with the N-Aβ fragment alone (P < 0.0001), ACh + N-Aβcore, or oAβ42 + N-Aβ fragment (P < 0.0001).
Homomeric α7-nAChR exposed to N-Aβ fragment alone exhibited significantly longer total burst durations over α7-nAChR exposed to ACh alone, oAβ42 alone, or N-Aβcore alone (Figure 4D; P < 0.0001) or when compared to α7-nAChR exposed to ACh + N-Aβ fragment or oAβ42 + N-Aβ fragment (P > 0.0001). Interestingly, α7-nAChR burst duration was greater in the presence of ACh + N-Aβ fragment than in the presence of ACh alone (P > 0.05). Homomeric α7-nAChR burst duration also is increased in the presence of oAβ42 + N-Aβ fragment compared to effects of oAβ42 alone (P < 0.05), and the latter was not significantly different from that of oAβ42 + N-Aβcore (P > 0.05). The effects on α7-nAChR open-dwell times within bursts and total burst duration demonstrate the ability of the N-Aβ fragment to enhance these features alone or in combination with ACh or oAβ42.