GAP JUNCTION CHANNELS - DISTINCT VOLTAGE-SENSITIVE AND VOLTAGE-INSENSITIVE CONDUCTANCE STATES

All mammalian gap junction channels are sensitive to the voltage diffe rence imposed across the junctional membrane, and parameters of voltag e sensitivity have been shown to vary according to the gap junction pr otein that is expressed. For connexin43, the major gap junction protei n in the cardiovascular system, in the uterus, and between glial cells in brain, voltage clamp studies have shown that transjunctional volta ges (V-j) exceeding +/-50 mV reduce junctional conductance (g(j)). How ever, substantial g; remains at even very large V-j values; this resid ual voItage-insensitive conductance has been termed g(min). We have ex plored the mechanism underlying g(min) using several cell types in whi ch connexin43 is endogenously expressed as well as in communication-de ficient hepatoma cells transfected with cDNA encoding human connexin43 . For pairs of transfectants exhibiting series resistance-corrected ma ximal g(j) (g(max)) values ranging from <2 to >90 nS, the ratio g(min) /g(max) was found to be relatively constant (about 0.4-0.5), indicatin g that the channels responsible for the voltage-sensitive and -insensi tive components of g, are not independent. Single channel studies furt her revealed that different channel sizes comprise the voltage-sensiti ve and -insensitive components, and that the open times of the larger, more voltage-sensitive conductance events declined to values near zer o at large voltages, despite the high g(min). We conclude that the vol tage-insensitive component of g(j) is ascribable to a voltage-insensit ive substate of connexin43 channels rather than to the presence of mul tiple types of channels in the junctional membrane. These studies thus demonstrate that for certain gap junction channels, closure in respon se to specific stimuli may be graded, rather than all-or-none.