From overshoot to voltage clamp

when we were both living in Trinity College, Cambridge. He finished as an undergraduate in 1935 and was a research scholar and, from 1936, a Junior Research Fellow; I came up as an undergraduate in 1935. In the summer of 1939, he went to the marine laboratory at Plymouth to do experiments on the giant nerve fibres of squid. He invited me to join him, which I did at the beginning of August; we left on 30 August because war was obviously imminent. Finding the overshoot We had been brought up on the theory of Bernstein [1], according to which the action potential is due to the membrane suddenly becoming permeable to all ions, so that the potential difference across the membrane would fall from its resting value to near zero. This permeability increase had been confirmed experimentally by Kacy Cole and Howard Curtis [2] (Fig. 1). Hodgkin had a hint, from experiments on single nerve fibres of crabs and lobsters, that the action potential might be larger than the resting potential, so that the membrane potential would actually reverse. However, this was uncertain (because it was based on recordings with external electrodes) and was not published until later [3]. At Plymouth, we pushed an electrode down inside squid fibres and found that this was true: at rest the interior was ~−45 mV but at the peak of the action potential it was ~+40 mV. We published this result in a short letter to Nature [4], with no explanation for this ‘overshoot’. TRENDS in Neurosciences Vol.25 No.11 November 2002