Phospholipid Hydrolysis and [Ca²⁺]_i Control

Abstract

The existence of a direct link between receptor-activated phospholipid hydrolysis and changes of cellular Ca²⁺ homeostasis was hypothesized quite some time ago but remained unclear, being based largely on anecdotal evidence, until the discovery almost a decade ago of the specific Ca²⁺ release activity of inositol 1,4,5-trisphosphate (IP3) (reviewed by Berridge and Irvine, 1989). Initially, the reaction responsible for IP₃ generation, i.e., the hydrolysis of phosphatidyl inositol 4,5-bisphosphate (PIP₂) by specific phospholipase(s) C (PLC), was thought to be the only metabolic process by which [Ca²⁺]_i was regulated. However, the field soon became more complex. In 1984–85, activation of the receptors coupled to PPI hydrolysis was shown to stimulate not only Ca²⁺ release from internal stores but also Ca²⁺ influx via channels in the plasmalemma, later named second messenger-operated channels (Meldolesi and Pozzan, 1987). The multiplicity and complex regulation (not only by second messengers, but also via G proteins and the physiological state of intracellular Ca²⁺ stores) of these channels is discussed elsewhere (Meldolesi et al., 1991).

H. S. is a MRC-CNR Canada-Italy Exchange Scientist