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The Journal of Neuroscience, November 15, 1998, 18(22):9238-9244

A Memory for Extracellular Ca²⁺ by Speeding Recovery of P2X Receptors from Desensitization

S. P. Cook¹, K. D. Rodland², and E. W. McCleskey¹

¹ Vollum Institute L-474 and ² Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201-3098

Nerve endings of nociceptors (pain-sensing neurons) express an unusual subtype of ATP-gated ion channel, the P2X3 receptor, that rapidly desensitizes (<100 msec) and slowly recovers (>20 min). Here we show that Ca²⁺, or certain other polyvalent cations, binds to an extracellular site on rat sensory neurons and can increase current through P2X3 channels more than 10-fold. Importantly, Ca²⁺ facilitates P2X3 current to precisely the same level whether a transient Ca²⁺ change occurred just before or several minutes before activating the channels with ATP. This memory for past changes in Ca²⁺ is integrative in that a 90 sec Ca²⁺ stimulus delivered just before an ATP application has the same effect as an earlier series of three, separated 30 sec Ca²⁺ stimuli. These diverse phenomena are explained by a single mechanism: Ca²⁺ speeds recovery of P2X channels from desensitization. Recovery follows an exponential growth curve that depends on the duration, but not the timing, of changes in recovery rate. Modulation of desensitization underlies a well described short-term memory in bacteria, and it might be similarly used in the nervous system.

Key words: P2X3; purinergic; Ca²⁺; desensitization; recovery rate; rat; sensory neuron; nociceptor; learning; memory; short term memory; pain; hyperalgesia; dorsal root ganglia

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18229238-07$05.00/0

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