. Author manuscript; available in PMC: 2010 May 26.

Published in final edited form as: Nat Immunol. 2009 Jan;10(1):21–27. doi: 10.1038/ni.f.220

Table 1.

Routes of cytosolic Ca²⁺ modulation in lymphocytes

Route	Activation	Physiological outcome	Reference
Pumps
SERCA	ATP	Pumps Ca²⁺ from cytosol to ER	74
PMCA	ATP	Prevents cytosolic Ca²⁺ accumulation and contributes to Ca²⁺ signaling dynamics	75,76
Intracellular Ca²⁺ channels
Ins(1,4,5)P₃R, ER	Ins(1,4,5)P₃	Transient increase in cytosolic Ca²⁺	77
RyR	Ca²⁺, cADPR, L-type Ca²⁺ channels	Transient increase in cytosolic Ca²⁺	78,79
Ca²⁺-selective store-operated channels
CRAC	Store-operated	Sustained increase in cytosolic Ca²⁺	4–6
Nonselective (receptor- or store-operated) channels
TRPC	Diacylglycerol or store-operated?	Sustained increase in cytosolic Ca²⁺	7–9
Ion exchangers
Dual-mode sodium-calcium exchanger	Forward mode: high cytosolic Ca²⁺ concentrations	Prevents accumulation of Ca²⁺ in the cytosol	80,81
	Reverse mode: high cytosolic Na⁺ concentrations	Extrudes Na⁺ and contributes to increase in cytosolic Ca²⁺	76,81
Mitochondrial Ca²⁺ buffering
Ca²⁺-uptake channel: mitochondrial Ca²⁺ uniporter	High cytosolic Ca²⁺ concentrations	Buffers sub-plasmalemmal Ca²⁺	82,83
Ca²⁺-extrusion channel: sodium-calcium exchanger	High mitochondrial Ca²⁺ concentrations	Buffers sub-plasmalemmal Ca²⁺, facilitates ER refilling	82,83
Indirect modulators of cytosolic Ca²⁺
TRPM4 and TRPM5 (Na⁺ channels)	Membrane depolarization–activated	Inhibits the driving force for CRAC-mediated Ca²⁺ influx	52,54
Kv1.3 (K⁺ channel)	Membrane depolarization–activated	Potentiates the driving force for CRAC-mediated Ca²⁺ influx	84
KCa3.1 (K⁺ channel)	Calcium-activated	Potentiates the driving force for CRAC-mediated Ca²⁺ influx	84
Non-store-operated Ca²⁺ influx
Purinergic P2 receptors	Nucleotides	Nonselective cation influx	85
TRPV6 (CaT1)	Constitutively active; inhibited by cytosolic increase in Ca²⁺	Selective Ca²⁺ influx	1,86
TRPM2 (LTRPC2)	Pyrimidine nucleotides, ADPR and NAD	Nonselective cation influx	87,88
TRPM7 (MIC or LTRPC7)	Intracellular Mg²⁺ concentrations	Nonselective cation influx	89,90
ARC channel	Phosphorylation	Selective Ca²⁺ influx	91
Ins(1,4,5)P₃R, PM (controversial)	Ins(1,4,5)P₃	Unknown	92
Cav (controversial)	Unclear in lymphocytes	Contributes to increases in cytosolic Ca²⁺ and NFAT translocation	71,72

CaT1, Ca²⁺ transport protein; ADPR, adenosine 5′ diphosphoribose; NAD, nicotinamide adenine dinucleotide; LTRPC, long transient receptor potential channel; MIC, Mg²⁺ inhibited cation channel; PM, plasma membrane.