Analysis of the presence and physiological relevance of subconducting states of connexin43-derived gap junction channels in cultured human corporal vascular smooth muscle cells

Subconductance states are a commonly observed feature of gap junction chann els. Their overt frequency and consistent appearance in both single and mul tichannel records have led to speculation that they might be of physiologic al importance in terms of altering the rate of small solute transfer from c ell to cell. Among the connexin gene family, connexin43 (Cx43) is the most ubiquitous connexin that has been shown to generate subconductive states. T herefore, it was the explicit aim of this investigation to more fully evalu ate the potential contribution of human Cx43-derived subconducting states t o intercellular communication in cultured human corporal vascular smooth mu scle cells. To determine the weight of subconductive states in our records, we analyzed amplitude histograms of multichannel and single-channel data d uring the application of transjunctional voltages larger than expected for physiological conditions but still smaller than transjunctional voltages kn own to induce lower conductive states (V-o>V-j). The data clearly indicated that the subconducting states occupy only a small fraction of the total ch annel open time. This was reflected by the fact that the average open proba bility for the subconductive state(s) determined from the 9 records analyze d was approximate to 2%. Closer inspection of the data revealed that the fr equency of subconductive states was actually higher than the frequency of t he main state conductance. In summary, recording conditions sufficient for evaluation of the intrinsic gating characteristics of human Cx43-derived ga p junction channels have been used. Under these conditions, our data clearl y indicate that despite their greater frequency, the duration of subconduct ance events is so short relative to the main state duration as to render th em physiologically insignificant.