The effect of noradrenaline on the ion permeability of isolated mammalian hepatocytes, studied by intracellular recording.

1. The influence of noradrenaline on the membrane potential and conductance of isolated guinea-pig and rabbit hepatocytes in short-term (2-8 h) tissue culture has been studied by intracellular recording. 2. Resting hepatocytes had linear current-voltage relationships, with input resistances of 166 and 216 M omega in guinea-pig and rabbit cells respectively. The recorded membrane potential was -18 mV in each species, though the true resting potential is likely to have been up to 10 mV greater. 3. The hepatocytes sometimes slowly hyperpolarized during intracellular recording, and this was associated with a fall in membrane resistance, and an increase followed by a decrease in membrane potential noise. These effects were abolished by quinine (200 microM) but not by apamin (50 nM), and are attributable to a K+ conductance activated by cell swelling. 4. Noradrenaline (2 microM, in the presence of propranolol at 1 microM) was applied to individual hepatocytes by pressure ejection (puffer pipette technique). After a short latency, the cells hyperpolarized by a mean of 18 mV in both guinea-pig and rabbit preparations. This was associated with a large rise in membrane conductance (50 nS in guinea-pig, 54 nS in rabbit cells). The reversal potential for this action was -38 mV. 5. The experiments were repeated in the presence of apamin (50 nM) to block the Ca2+-dependent K+ permeability which noradrenaline activates in these cells. Noradrenaline still caused some hyperpolarization and a substantial increase (approximately 40 nS) in conductance, with a reversal potential (Er) of -31 mV. This can be attributed to an increase in Cl- conductance. 6. In keeping with this interpretation, noradrenaline applied in the absence of Cl- (replaced by isethionate or gluconate) caused a much greater hyperpolarization (58 mV in guinea-pig, 40 mV in rabbit cells) associated with a smaller rise in conductance (approximately 12 nS). Er for this action was -95 mV (guinea-pig) and -68 mV rabbit), suggesting that the conductance increase was now mainly to K+. 7. The magnitudes of the conductance changes produced by noradrenaline under the various experimental conditions suggest that the increase in the conductance to Cl- (delta GCl) is 3-fold greater than that to K+ (delta GK). 8. The activation of delta GCl occurs either at the same time as delta GK, or (in ca. one cell in ten) a few seconds later.(ABSTRACT TRUNCATED AT 400 WORDS)