A MEMORY FOR EXTRACELLULAR CA2+ BY SPEEDING RECOVERY OF P2X RECEPTORSFROM DESENSITIZATION

Nerve endings of nociceptors (pain-sensing neurons) express an unusual subtype of ATP-gated ion channel, the P2X3 receptor, that rapidly des ensitizes (<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 chan nels 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. Th is memory for past changes in Ca2+ is integrative in that a 90 sec Ca2 + stimulus delivered just before an ATP application has the same effec t as an earlier series of three, separated 30 sec Ca2+ stimuli. These diverse phenomena are explained by a single mechanism: Ca2+ speeds rec overy of P2X channels from desensitization. Recovery follows an expone ntial growth curve that depends on the duration, but not the timing, o f changes in recovery rate. Modulation of desensitization underlies a well described short-term memory in bacteria, and it might be similarl y used in the nervous system.