Properties of membrane ion conductances evoked by hormonal stimulation of guinea-pig and rabbit isolated hepatocytes

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Abstract
Membrane conductance changes evoked in isolated guinea-pig or rabbit hepatocytes by hormonal stimulation were studied with the whole-cell patch clamp technique. In Cl-containing solutions, noradrenaline (NA). ATP or angiotensin II (AII) evoked an increase of conductance to both K (G$_K$) and Cl (G$_{Cl}$) ions. Activation of G$_K$ occurred after a delay of several seconds and was sustained in the presence of hormone. Activation of G$_{Cl}$ was transient, lasting several seconds, and arose either at the same time or shortly after the increase in G$_K$. Conductances showed an initial rapid rise and slow oscillatory changes during maintained hormone application. The NA-induced current reversed at - 19 mV in Cl solutions, between the equilibrium potentials for chloride (E$_{Cl}$ = 0 mV) and potassium ions (E$_K$ = -85 mV), and at -75 mV, near E$_K$, in Cl-free solution. In both conditions whole-cell current-voltage curves were linear in the range -100 mV to +40 mV. The conductance increase produced by NA to Cl$^-$ ions was about 50 nS, that to K$^+$ ions was 6 nS. The potassium conductance increase was abolished by the polypeptide toxin apamin (50 nM). An increase in membrane current noise was associated with NA-evoked outward K$^+$ current and blocked by apamin. Spectral analysis gave estimates of the elementary K channel conductance of 1.7 pS. Power spectra were fitted by two Lorentzian components, with average half-power frequencies of 2 and 190 Hz. These results are discussed in relation to the single-channel properties and indicate that the open probability of K channels during the NA response is high. In Cl solutions, with apamin to block the K conductance, no increase in current noise was detected during the large Cl conductance evoked by NA. This suggests either that Cl channels are of very low unitary conductance (less than 1 pS) or that Cl transport is due to a membrane carrier The complex time-course of hormonally evoked conductances is not due to the properties of ion conductances per se but probably to underlying changes of intracellular second-messenger concentration.