Ions in smooth muscle, now and then

Edith Bulbring is widely regarded as a pioneer in the smooth muscle field – driving forward understanding of electrophysiology and inspiring the next generation of investigators. In September 2005 there was a meeting in Oxford to celebrate the contributions of two of these investigators – Tom Bolton and Alison Brading, who met in Oxford under Edith's tutorage. Although not publishing together they have been spirited contemporaries and provided us with almost the same number of original research papers each. Between them they have so far published 126 papers in The Journal of Physiology, work that has attracted 824 citations. Tom's most cited paper is on spontaneous transient outward currents in smooth-muscle cells (Benham & Bolton, 1986), while Alison's is one of her earliest papers on CoEDTA in smooth muscle (Brading & Jones, 1969). Tom and Alison are now household names in the field and remain active contributors. Mike Kotlikoff started off the scientific programme of the Meeting with a talk on ‘calcium indicator mice’, showing striking images of intracellular calcium measured in vivo. This was to set the scene for talks on various aspects of calcium signalling in smooth muscle by Dima Gordienko, Mark Evans, Yuji Imaizumi and Casey van Breemen. Coupled with this we saw studies exploring endogenous cationic channels and transient receptor potential channels by Sasha Zholos, William Large, Ryuji Inoue, Seiichi Komori, Chris Benham, Phil Aaronson and Bernd Nilius. Kenton Sanders gave the Smooth Muscle Special Interest Group Lecture, Diomedes Logothetis the Ion Channel Lecture – showing two extremes, from the origins of rhythmicity in the gut, to the molecular basis of PIP2 regulation of an array of membrane proteins including channels. The theme of physiological rhythmicity was taken up by Sue Wray, Mark Hollywood, Hikaru Suzuki and Tom Bolton. Steffen Hering gave us an intriguing overview of the still-unsolved mechanism of action of calcium antagonists, while there were also new insights into transcriptional control mechanisms, by Karen Lounsbury and David Beech, and insightful talks on the functions, complexities and diversity of potassium channels by Rick Lang, Alison Gurney and Ligia Toro. In this themed edition of The Journal of Physiology we are fortunate to have a series of excellent and concise reviews from established as well as up-and-coming investigators in the field. The reviews provide a flavour and formal record of the meeting and also a glimpse into the continuing vibrancy of the field, recent advances, and questions remaining unsolved. Brading (2006), McHale et al. (2006), Noble et al. (2006) and Sanders & Koh (2006) focus on mechanisms of rhythmicity in various visceral organs. Underlying platforms of calcium-release events and calcium-activated channels predominate, while Sanders & Koh (2006) expand on their hypothesis for the role of K2P potassium channels in periods of quiescence. There is also the topical thread of interstitial cells and their integration in smooth muscle tissues. Bolton (2006) provides an elegant commentary on elementary calcium-release events, while Albert & Large (2006) develop hypotheses for second messenger pathways regulating calcium- and sodium-permeable channels. Aaronson et al. (2006) provide a thoughtful review of mechanisms underlying hypoxic pulmonary vasoconstriction, a subject that has consumed the attention of many investigators in the smooth muscle field and yet retained significant unanswered questions and areas of controversy. Barlow et al. (2006) and Lu et al. (2006) provide a distinctly molecular perspective, poised in physiological contexts. Barlow et al. (2006) pioneer studies of the link between smooth muscle excitation and transcriptional activity, emphasizing the importance of calcium entry for gene expression as well as regulation of contraction and electrical rhythmicity. Lu et al. (2006) will have especially broad appeal, providing an important and surprisingly rare summary of the protein partners and regulation of the BKCa potassium channel – an old favourite in smooth muscle, but also major player in other cell types. It is hoped that the selection of reviews will provide a useful introduction for those outside the field and raise challenging questions for those already actively engaged or considering joining. Humans and many other animals would be lost without their many tubes and reservoirs, precisely regulated by the smooth muscle cell in its many guises. Despite profound advances in our understanding of these cells key questions remain unanswered and enormous facets of their origin, survival, phenotype and behaviour are mysterious or simply completely unexplored.