A lifetime’s adventure in extracellular K+ regulation: the Scottish connection

In a career that has spanned 45 years and shows no signs of slowing down, Dr Bruce Ransom has devoted considerable time and energy to studying regulation of interstitial K+. When Bruce commenced his studies in 1969 virtually nothing was known of the functions of glial cells, but Bruce’s research contributed to the physiological assignation of function to mammalian astrocytes, namely interstitial K+ buffering. The experiments that I describe in this review concern the response of the membrane potential (Em) of in vivo cat cortical astrocytes to changes in [K+]o, an experimental manoeuvre that was achieved in two different ways. The first involved recording the Em of an astrocyte while the initial aCSF was switched to one with different K+, whereas in the second series of experiments the cortex was stimulated and the response of the astrocyte Em to the K+ released from neighbouring neurons was recorded. The astrocytes responded in a qualitatively predictable manner, but quantitatively the changes were not as predicted by the Nernst equation. Elevations in interstitial K+ are not sustained and K+ returns to baseline rapidly due to the buffering capacity of astrocytes, a phenomenon studied by Bruce, and his son Chris, published 27 years after Bruce’s initial publications. Thus, a lifetime spent investigating K+ buffering has seen enormous advances in glial research, from the time cells were identified as ‘presumed’ glial cells or ‘silent cells’, to the present day, where glial cells are recognised as contributing to every important physiological brain function

A molecular mechanism for long-term sensitization in Aplysia.

Sensitization of the gill- and siphon-withdrawal reflex in Aplysia is thought to result from a set of molecular processes with different time courses: short-term sensitization is explained by cyclic AMP-dependent modulation of ion-channel function in sensory neurons lasting minutes; memory that endures for hours or longer, by the expression and distribution within the neurons of new gene products. Because gene induction and axonal transport are relatively slow, there may also be a need for a distinct form of intermediate memory to bridge the short- and long-term processes. We now report that a protocol producing long-term sensitization results in a decrease in the amount of regulatory subunits of the cAMP-dependent protein kinase in animals 24 h after training, with no effect on the catalytic subunit. The loss appears to be post-translational. Because a decrease in the ratio of regulatory to catalytic subunits would result in elevated kinase activity after cAMP has returned to its unstimulated concentration in sensory cells, it could be the molecular mechanism of intermediate memory