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Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London.

1. The action of noradrenaline on cells isolated from the rabbit ear artery was studied with the whole-cell configuration of the patch clamp technique. In normal potassium-containing solutions at a holding potential of -50 mV noradrenaline elicited either outward, inward or mixed outward and inward currents. These responses were blocked by the alpha-adrenoceptor antagonist, phentolamine (10(-6) M). 2. The outward current occurred as a consequence of an increase in membrane conductance and the reversal potential was close to the potassium equilibrium potential (EK). It was possible to record outward currents without external calcium but not when the concentration of EGTA in the pipette was increased to 10 mM or when potassium was absent from the pipette solution. It is concluded that the outward current evoked by alpha-adrenoceptor stimulation is produced by a calcium mediated increase in potassium conductance. 3. The ionic basis of the inward current was investigated in potassium-free external and pipette solutions. When sodium chloride was the major constituent of the external and pipette solutions the reversal potential (Er) of the noradrenaline-induced current was 0.63 mV, close to ENa and ECl. 4. When most of the external sodium chloride was replaced by sucrose Er was intermediate between ENa and ECl but had shifted significantly towards ENa. Further ion substitution experiments suggest that noradrenaline increased the membrane conductance to both anions and cations. 5. When the current was carried predominantly by anions, depolarizing steps (from -50 mV) produced outward current relaxations with a time constant of about 40 ms. Bath-applied caffeine also produced a membrane current which rectified in the outward direction. 6. When the response to noradrenaline was mediated mainly by cations, the relationship between the membrane current and clamp potential was non-linear and the amplitude of the currents at potentials positive to -50 mV became disproportionately smaller. In addition on repolarization to -50 mV the instantaneous current was followed by an inward relaxation. 7. In high external barium solution noradrenaline evoked a membrane current with a reversal potential much more positive than ENa or ECl. This current was recorded in the presence of 10(-5) M-nifedipine and diltiazem and in 10(-4) M-cadmium which suggests that the voltage-dependent calcium channel is not implicated in the generation of the non-selective cation current to noradrenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

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