Calcium oscillations in non-excitable cells

Abstract

but rather repetitive rises in cytosolic free Ca 2+ ([Ca2+]i), stimulated by vasopressin in hepatocytes (Fig. 1A) or histamine in endothelial cells (Fig. 1B), or from a recently published model of receptor- mediated [Ca.,+]i oscillations (Fig. 1C). Not only has [Ca2+]i replaced mV on the vertical axis, but the time axis is in minutes rather than tens of milliseconds; and these are signals generated in non-excitable ceils, i.e. cells that do not have action potentials. These patterns mirror the conversion of an ampli- tude-modulated stimulus into a digital code, so well-known to neuroscientists, for instance with generator potentials producing trains of spikes at sensory nerve endings or constant depolarization evoking repetitive spikes in a motor neurone. There is even a suggestion of a 'pace-maker' rise in [Ca2+] i prior to the rapid upstroke in Fig. 1B and C. The original description of the all-or-nothing law came from E. D. Adrian's work on signal transmission along axons where the frequency and pattern of essentially invariant action poten- tials gives faithful coding over long distances. But we also know that the amplitude and shape of an action potential can be important in the transduction of information, for example when presynaptic inhi- bition reduces spike height and thereby reduces transmitter re- lease, or when the changing dur- ation of a cardiac action potential changes the strength and duration of a systolic contraction. Similar mechanisms are now being un- covered as oscillating [Ca2+]i sig- nals are investigated in non-excit- able cells. It is of course expected that action potentials will evoke spikes of [Ca2+]i in cells with significant voltage-gated Ca .,+ entry, or inter- nal release controlled by mem- brane potential as in skeletal mus- cle. Such spikingin [Ca2+]i has been indirectly monitored in neurones by measuring Ca2+-activated K + conductance, or in muscle by measuring contraction, and more recently by direct measurements of [Ca2+]i with indicator dyes or photoproteins. However, it is only