Channel functionality is necessary for Cx37-mediated cell death. (A) Cx37-WT and -S275D form functional GJChs with comparable junctional conductance. No evidence of coupling was apparent between cells expressing Cx37-T154A-S321D. Cx37-WT: 3.38 ± 0.7 nS, N = 30; -S275D: 4.25 ± 0.8 nS, N = 19; -T154A S321D: 0 nS, N = 8. * p < 0.05 vs WT. (B) Representative current trace of Cx37-S275D comprised GJChs showing a high frequency of 220–260 pS transition events. Grey arrow: start of 25 mV pulse. (C) Transition amplitude frequency plots for Cx37-WT (black) and -S275D (orange) GJChs suggest an increased preference for large amplitude transitions in iRin37-S275D cells. Cx37-WT N = 11, n = 1235; -S275D N = 6, n = 596. (D) Despite expression (dox +), iRin37-T154A-S321D cells (green) proliferate. n = 4 in triplicate for each isoform. Inset: Cx37-T154A-S321D eliminates the induced cell death and growth arrest characteristic of Cx37-WT expressing cells. All values are mean ± s.e.m (where error bars are not evident, they are smaller than the symbol size). p < 0.05 for dox + versus dox − for WT (∗) but not -T154A-S321D.