The effect of external pH (pHo) on the membrane potential and resistance of unfertilized zona-free hamster eggs was investigated by intracellular recording techniques. 2. A hyperpolarization of the hamster egg membrane was induced by raising the extracellular pH above 8.0. This hyperpolarization was accompanied by a rise in membrane conductance and was reversible by washing the egg. 3. The estimated value of the reversal potential of the hyperpolarizing response to a solution with pHo 9.5 was about -85 mV. The membrane potential changed linearly with log [K+]o with a slope of 43 +/- 2 mV (mean +/- S.D.; n = 4) for a 10-fold change in [K+]o, while it was unaltered by the removal of Cl- from the solution. 4. The amplitude of the pHo-induced hyperpolarization decreased substantially as [Ca2+]o was lowered from 20 to 1 mM. Sr2+ could substitute for Ca2+ in sustaining the response to high pHo, whereas Ba2+ or Mg2+ could not. 5. Injection of the Ca2+ chelator EGTA into the egg prevented the pHo-induced hyperpolarization suggesting that a rise in [Ca2+]i is required. 6. The rate of rise of Ca2+ action potentials was reversibly enhanced by raising pHo. However, influx through the voltage-gated Ca2+ channels is not involved in initiation and maintenance of the pHo-induced response, as responses were not affected by the Ca2+ channel blocker La3+. 7. The duration of the hyperpolarization evoked by intracellular Ca2+ injection in eggs bathed in normal solution or Na+-free solution was greatly prolonged by raising pHo. 8. It is suggested that a rise in external pH produces an increase in [Ca2+]i, activating a Ca2+-mediated K+ conductance which hyperpolarizes the egg membrane. 9. It is concluded that both a Na+-Ca2+ exchange system and a Ca2+ pump are responsible for Ca2+ extrusion and that inhibition of the Ca2+ pump by high pHo is the chief mechanism underlying the pH-induced hyperpolarization in hamster eggs. Although the Na+-Ca2+ exchange system is facilitated at high pHo, the effect of this facilitation of efflux is outweighed by the inhibition of the Ca2+ pump.
