Robert Meech, University of Bristol, UK

Ian Forsythe, University of Leicester, UK

Noel Davies, University of Leicester, UK

https://doi.org/10.36866/pn.119.50

Nick Standen is probably best known for uncovering the mechanism of action of vasodilators used for the treatment of hypertension and heart failure. This study, started when he was on research leave in Mark Nelson’s laboratory at the University of Vermont in 1987, showed that adenosine triphosphate-sensitive potassium (KATP) channels in arterial smooth muscle open in the presence of the vasodilator cromakalim. Cromakalim was known to relax airway, intestinal, and uterine smooth muscle and so KATP channels were probably physiologically active in many smooth muscle types (Standen et al., 1989). Nick Standen and Peter Stanfield, co-founders of the renowned Ion Channel Group at the University of Leicester, together with Austen Spruce had already shown that KATP channels were present in frog muscle membranes but it was hard to establish that they operated under physiological conditions. The link to the high potassium permeability seen during rigor displaced the hypothesis that it was caused by increased cellular calcium. This idea had arisen from the discovery of calcium activated potassium currents by Nick and his PhD supervisor Rob Meech, reported to the Physiological Society in 1974. 

Perhaps less well known is Nick Standen’s key role in understanding mechanisms of calcium channel inactivation. Nick had explored the voltage sensitivity of the mechanism during the course of his PhD work but recent studies suggested it might depend not on membrane potential directly, but on calcium ion entry. Whether it was a consequence of the passage of calcium across the cell membrane or of increased levels of intracellular calcium was as yet unknown. Nick showed that inactivation of this pathway could be produced by direct injection of calcium into the cell (Standen, 1981). Then he, Tim Plant and Tom Ward, excluded possible side effects of cellular acidification and presented a simple model in terms of calcium binding to intracellular sites. 

This survey cannot do justice to the sheer volume of Nick Standen’s output but a recurring theme is the link between membrane channels and cell metabolism. Both calcium activated potassium currents and calcium dependent calcium inactivation provide a direct link between neuronal activity and the metabolic processes that regulate intracellular calcium; in the case of KATP channels Nick was intrigued by possible links between metabolic factors and the regulation of blood flow.

Establishing a physiological role for KATP channels gave Nick the greatest satisfaction for he was essentially a practical person who wanted most of all to solve medical problems.  His sister Olivia recalls that in his early life he was greatly influenced by his grandfather who farmed near the family home in Oxford. It was his grandfather who taught him how to shoot and skin rabbits and let him capture wild animals. At one time his pets consisted of a vole, a weasel, a shrew and a mouse, all of which he kept in his bedroom. He studied the nocturnal behaviour of the mouse by rigging up an electric circuit to signal each time the animal left its cage. He wanted to add a ferret to his menagerie but his good-natured parents drew the line at that. He conducted a persistent campaign, endlessly dropping the word “ferret” into the conversation, but determination was clearly inherited and the parents never weakened. Instead Nick made do with a magpie, and the numerous guinea pigs that he sold to local pet shops. In his adult life he enjoyed mountaineering, rock climbing and deer stalking. 

Nick’s skills as an experimentalist contributed to the success of the highly influential Microelectrode Techniques Course at Plymouth Marine Station and he was an editor (with Peter Gray and Michael Whitaker) of the first edition of its Handbook. No one could collaborate with Nick without becoming a friend. His relaxed manner but forceful intellect earned respect from colleagues and students alike, and this was sustained by a keen work ethic. He was loyal and supportive to his research staff, endlessly fighting for funding to maintain their posts.  Undergraduate students appreciated his enthusiastic teaching, and he was keen to ensure they always received the best training. His intellect and his efficient deployment of it, his practical skills and his determination were clear from childhood, impressed his teachers at Cambridge and were recognized by everyone who met him.  

Nick’s forced retirement due to ill health was a tremendous loss, not only to his friends and colleagues but also to science in general. Among the honours he received, were the G.L. Brown Prize Lecture in 1990/91 and the International Prize Lecture in 2001. From 1991-94 he was Chairman of the Editorial Board of The Journal of Physiology.  He was elected to the Academy of Medical Sciences in 2001 and was made an Honorary Member of The Physiological Society in 2010.

Nick Standen was born on Dec 8th 1949 in Oxford, went to the Dragon School and then Magdalen College School. In 1971 he was awarded a First class degree in Natural Sciences while at Queens College Cambridge. After PhD studies in the Zoology Department, Cambridge and a brief period at Nottingham, he was appointed in 1976 to a lectureship at Leicester and remained there until retirement in 2009. His wife Alison and his three children, Jonathan, Claire and Jessica, sustained him during a prolonged period of poor health. As a father they remember him as being “oodles of fun”. He died on April 2nd 2020 following a respiratory tract infection. 

References

Standen, N.B. (1981). Nature 293, 158-159.

Standen, N.B., Quayle, J.M., Davies, N.W., Brayden, J.E., Huang, Y. and Nelson, M.T. (1989). Science 245, 177-180.