A voltage-sensitive persistent calcium conductance in neuronal somata of Helix

Abstract

1. An intracellular voltage clamp in conjunction with a patch pipette utilizing feed-back to monitor local current from the soma membrane were used to analyse transient and stationary currents in bursting pacemaker neurones in Helix pomatia and H. levantina. 2. A weak, net inward current flows during small (less than or equal 20 mV) depolarizations. This current exhibits slow activation kinetics, persistence during prolonged depolarization, and slow turning off at end of depolarization. Consequently, the steady-state current-voltage curve exhibits a region of negative resistance from about -55 to -35 mV. 3. The slow inward current and the negative resistance characteristic are rapidly and completely abolished by substitution of Co2+ or La3+ for Ca2+ and are partially blocked by the Ca-blocking drug D-600. Substitution of Tris or glucose for Na+ significantly reduces the inward current only after 15-20 min exposure, recovery being equally slow. 4. The inward current and the negative resistance characteristic of the I-V curve are greatly enhanced by Ba2+ substitution for Ca2+. This is ascribed in part to Ba2+ carrying current through the slow inward current channels and in part to a suppression of the late K+ current by Ba2+. 5. The inward current is also present in many non-bursting neurones but fails to appear as a net inward current due to short circuiting by a leakage current or by the delayed potassium current. In these cells the slow inward current contributes to inward going rectification. Replacement of Ca2+ with Ba2+ enhances the current so as to produce a net inward current during small depolarizations in these neurones. 6. It is concluded that the slow inward current is carried primarily by Ca2+ in the soma membrane of bursting pace-maker neurones and a number of non-bursting cells examined in the parietal ganglion of Helix. 7. The sensitivity to small depolarizations and persistence during prolonged depolarization suggests two roles for the Ca system in the generation of slow pace-maker oscillations. In this model the Ca system contributes to the slow depolarization which constitutes the onset of the pace-maker wave, and also contributes to the increment in [Ca] in which activates the Ca-sensitive K+ conductance responsible for repolarization. The inhibition of spontaneous bursting by Ca-blocking agents supports this model.