Ricardo Miledi. 15 September 1927—18 December 2017

Abstract

For nearly five decades, Ricardo Miledi was among the foremost researchers in elucidating how nerves transmit signals across synapses. Born in Chihuahua, Mexico, he qualified as a medical doctor, obtained a PhD with Arturo Rosenblueth and then, while in Canberra with John Eccles FRS, was invited by Bernard Katz FRS to join the Biophysics department at University College London, where he stayed from 1958 to 1984. Both independently and with Katz, he demonstrated that influx of calcium into the presynaptic nerve terminal is the essential trigger for the release of the neurotransmitter that carries signals across to the postsynaptic cell. He found that cutting the nerve to a frog's muscle increased the number and distribution of its muscle acetylcholine (ACh) receptors, which he purified and established as membrane proteins. Together with Katz, he introduced the technique of membrane noise analysis to determine the properties of the individual ion channels opened by ACh, providing the first functional characterization of a single receptor with integral ion channel. With Eric Barnard (FRS 1981), he pioneered a new approach facilitating the study of neurotransmitter receptors and ion channels by ‘transplanting’ them from brain and other tissues into large Xenopus oocyte cells by injection of messenger RNA. After moving to the University of California, Irvine, in 1984, he helped to establish the Mexican Institute for Neurobiology at Querétaro. Working in Irvine and Mexico he extended this oocyte expression technique to incorporate transplanted brain membranes, particularly from patients with epilepsy or other neurological disorders. He received many honours for his work, including the Royal Medal (1998), but was happiest working in his lab applying his extraordinary technical skills and imagination to study synaptic transmission and inspiring a generation of neuroscientists.