Gap Junctional Conductance Is a Simple and Sensitive Function of Intracellular <i>p</i> H

TLDR

The cytoplasmic pH (pHi) of amphibian and teleost blastomeres is approximately 7.7. Gap junction closure at low pHi is a cooperative process involving multiple charged sites on the channel macromolecules. Acidification rapidly and reversibly reduces junctional conductance following a Hill relationship (K≈50 nM, pK≈7.3, n≈4–5) that is identical for rising and falling pHi, shows no hysteresis, and indicates protons act directly on the channel.

Abstract

The p H of the cytoplasm ( p H i ) measured with p H-sensitive microelectrodes in cleavage-stage blastomeres of amphibian ( Ambystoma ) and teleost ( Fundulus ) embryos is about 7.7. In electrotonically coupled cell pairs, junctional conductance is rapidly and reversibly reduced by acidification of the cytoplasm. The relation between junctional conductance and p H i is the same for increasing and decreasing p H and is independent of the rate of change over a wide range. The relation is well fitted by a Hill curve with K = 50 n M (p K = 7.3) and n = 4 to 5. The closure of gap junction channels at low p H i appears to be a cooperative process involving several charged sites. The absence of hysteresis and identity of effects for fast and slow p H i changes implies that protons act directly on the channel macromolecules and not through an intermediate in the cytoplasm.