Table 1.

Cytosolic Ca²⁺ regulatory mechanisms in lymphocytes

Mechanism	Biochemical action	Main cell physiological roles	Reference
Active transport
SERCA pumps	Pumps Ca2+ from the cytosol into ER	Maintain ER stores of Ca2+; shape Ca2+ signals	114
PMCA pumps	Pumps Ca2+ from the cytosol to outside the cell	Shape Ca2+ signals; limit total cellular Ca2+ accumulation	18,115
Exchange transport
Na+/Ca2+ exchangers	Direct mode: exchange cytosolic Ca2+ for Na+ during high cytosolic Ca2+ accumulation	Limit total cellular Ca2+ accumulation	reviewed in 113
	Reverse mode: exchange of cytosolic Na+ for extracellular Ca2+	Mechanism for Ca2+ entry in response to accumulation of cytosolic Na+	reviewed in 113
Mitochondrial uptake
Unknown mitochondrial ion channel	Ion channels that allows primarily electrical gradient-driven diffusion of Ca2+ from ER to mitochondrial matrix	Transient buffering of cytosolic Ca2+ during acute elevations	116,117, reviewed in 118,119
Mitochondrial extrusion
Unknown Na+-or H+-gradient-driven active transporters	Exchangers that extrude accumulated Ca2+ from mitochondrial matrix once cytosolic Ca2+ falls	Buffering of the decreasing phase of a Ca2+ signal via gradual release of Ca2+ to the cytosol	reviewed in 119,120
Passive diffusion
InsP3 receptors	Ion channels which allow passive chemical-gradient-driven diffusion of Ca2+ from ER to cytosol	Transient acute elevations in cytosolic Ca2+	Reviewed in 121
Plasma membrane Ca2+ channels	Ion channels that allow passive chemical and electrical-gradient-driven diffusion of Ca2+ from ER to cytosol	Transient and sustained elevations in cytosolic Ca2+; replenishment of total cellular Ca2+	See for example 2,3,6

SERCA, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase; PMCA, plasma membrane Ca²⁺ ATPase; ER, endoplasmic reticulum; InsP₃; inositol-1,4,5-triphosphate;