Cumulative Inactivation Research Articles

Inactivation of delayed outward current in molluscan neurone somata.

1. Inactivation of delayed outward current was studied by voltage clamp of isolated neurone somata of the molluscs Archidoris and Anisodoris. During prolonged voltage clamp steps in normal artificial sea water delayed outward current rises to a peak and then declines to a non-zero steady-state. During repetitive clamp pulses at repetition rates slower than 2/sec, the amplitude of peak outward current in the second pulse is commonly less than the amplitude at the end of the preceding pulse, giving the impression of continued inactivation during the repolarized interval. We have termed this property cumulative inactivation. 2. Two components of delayed outward current were separated using tetraethyl ammonium ions (TEA) and cobalt ions (Co). External TEA blocks 90% of a voltage and time dependent outward current termed K current (IK). External Co blocks 85% of a Ca activated delayed outward current termed Ca current (ICa does not inactivate during prolonged or repetitive voltage clamp pulses. IK, however, inactivates during prolonged voltage clamp steps and shows cumulative inactivation during repetitive voltage clamp pulses. 3. Inactivation of IK is voltage and time dependent and does not require influx of Ca ions. 4. As measured by a prepulse method, the onset of inactivation is characterized by a two time constant process. Fast inactivation occurs with a time course comparable to the rate of rise of outward current and can account for 90% of total inactivation. 5. Recovery from inactivation is slow with a time constant approximately an order of magnitude slower than the onset of inactivation. 6. The current-voltage (I-V) curve for peak IK can be N-shaped, with a region of negative slope resistance in the range of +30 to +80 mV. The I-V curve for steady-state IK, however, shows little or no tendency to form a local maximum. 7. The pattern of delayed outward current varies considerably between cells. A major contributing factor to this variability appears to be the relative contributions of ICa and IK to delayed outward current.