Properties of membrane ion conductances evoked by hormonal stimulation of guinea-pig and rabbit isolated hepatocytes.
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 (GK) and Cl (GCl) ions. Activation of GK occurred after a delay of several seconds and was sustained in the presence of hormone. Activation of GCl was transient, lasting several seconds, and arose either at the same time or shortly after the increase in GK. 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 (ECl = 0 mV) and potassium ions (EK = -85 mV), and at -75 mV, near EK, 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.
Capiod
T
T
Department of Pharmacology, University College London, U.K.
Ogden
D C
DC
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D004553:Electric Conductivity; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits
D002712:Chlorides; D000255:Adenosine Triphosphate; D011433:Propranolol; D009638:Norepinephrine