Table 2.
Effects of phosphoinositides on ion channels and transporters
| Channel | Ins Lipid Regulator | Reference Nos. |
|---|---|---|
| Voltage-gated Ca2+ channels | ||
| T-type channels | ??? | No reports |
| L-type channels | PtdIns(4,5)P2 (+) | 1038, 1490, 1491, 1815 |
| N-type channels | PtdIns(4,5)P2 (+) | 487, 865 |
| P/Q-type channels | PtdIns(4,5)P2(±) | 1302, 1735 |
| TRP channels | ||
| TrpL (Drosophila)* | PtdIns(4,5)P2(−) | 410, but (+) 662 |
| TrpC1 | PtdIns(4,5)P2(+) | 1331 |
| TrpC3 | PtdIns(4,5)P2(+) | 883 |
| TrpC4a | PtdIns(4,5)P2(−) | 1180 |
| TrpC5 | PtdIns(4,5)P2(±) | 782, 1573 |
| TrpC6 | PtdIns(4,5)P2(+) | 883, but (−) 27, 742 |
| TrpC7 | PtdIns(4,5)P2(+) | 883, but (−) 742 |
| TrpM2 | PtdIns(4,5)P2(+) | 1568 |
| TrpM4 | PtdIns(4,5)P2(+) | 1137, 1811 |
| TrpM5 | PtdIns(4,5)P2(+) | 923, 1284 |
| TrpM6 | PtdIns(4,5)P2(+) | 1745 |
| TrpM7 | PtdIns(4,5)P2(+) | 1312, but see 850, 1515 |
| TrpM8 | PtdIns(4,5)P2(+) | 319, 922, 1284 |
| TrpV1** | PtdIns(4,5)P2, PtdIns4P (±) | 257, 559, 951, 1587 |
| TrpV2 | PtdIns(4,5)P2(+) | 1033 |
| TrpV3 | PtdIns(4,5)P2(−) | 365 |
| TrpV5 | PtdIns(4,5)P2(+) | 869, 1284 |
| TrpV6 | PtdIns(4,5)P2(+) | 1556, 1789 |
| TrpA1 | PtdIns(4,5)P2(−) | 783, but (+) 761 |
| TrpP2 | PtdIns(4,5)P2(−) | 961 |
| Cyclic nucleotide-gated channels | ||
| Hyperpolarization-activated HCN2 channels | PtdIns(4,5)P2(+) | 1220, 1826 |
| Cyclic nucleotide-gated (CNG) | PtdIns(3,4,5)P3 (−) | 177, 181, 1724, 1793 |
| ICRAC/Orai1 channels | PtdIns4P ???(+) | 184, 820 |
| Potassium channels | ||
| ROMK1 (Kir1.1) | PtdIns(4,5)P2(+) | 661, 915 |
| IRKs (Kir2.x) | PtdIns(4,5)P2(+) | 807, 1281, 1283, 1795 |
| GIRK (Kir3.x) | PtdIns(4,5)P2(+) | 661, 807, 1495 |
| KATP (Kir6.x) | PtdIns(4,5)P2, PtdIns(3,4,5)P3, PtdIns(3,4)P2 | 423, 616, 1283 |
| Two pore | PtdIns(4,5)P2(+) | 937, but see 245, 911 |
| Voltage-gated (Kv1.3) | PtdIns(4,5)P2, PtdIns(3,4,5)P3 (−) | 1012 |
| M-type (KCNQ2,3,5) | PtdIns(4,5)P2(+) | 422, 1488, 1794 |
| BK (Ca2+ activated) | PtdIns(4,5)P2(+) | 1598 |
| Ion exchangers and transporters | ||
| Na+/Ca2+ exchanger | PtdIns(4,5)P2(+) | 58, 588, 616, 1763 |
| Na+/H+ exchanger | PtdIns(4,5)P2(+) | 12 |
| Na+/HCO3− cotransporter | PtdIns(4,5)P2(+) | 1734 |
| Epithelial sodium channel (ENaC) | PtdIns(4,5)P2, PtdIns(3,4,5)P3 (+) | 960, 1229, 1230, 1564, 1787 |
| CFTR | PtdIns(4,5)P2(+) | 619 |
| Ion pumps | ||
| PM Ca2+-ATPase | PtdIns(4,5)P2(+) | 249, 438, 1132, 1192 |
| Ligand-gated channels | ||
| P2X1 | PtdIns(4,5)P2(+) | 126 |
| P2X2 | PtdInsP, PtdIns(4,5)P2(+) | 474 |
| P2X2/3 | PtdIns(4,5)P2, PtdIns(3,4,5)P3 (+) | 1074 |
| P2X4 | PtdIns(4,5)P2, PtdIns(3,4,5)P3 (+) | 126 |
| P2X5 | PtdIns(4,5)P2(+) | 127 |
| P2X7 | PtdIns(4,5)P2(+) | 127, 291 |
| NMDA | PtdIns(4,5)P2 (+) | 977 |
| NR1/NR2 | PtdIns(4,5)P2 (+) | 1037 |
The Drosophila TrpL channels are stimulated after PLC activation, but the signal responsible for the stimulation is highly debated. DAG and polyunsaturated fatty acids (PUFA) have been the most accepted stimuli (573), and in some cases it is speculated that the PtdIns(4,5)P2 decrease and proton accumulation contributes to their activation (662). However, several data indicate that these channels still need PtdIns(4,5)P2 for optimal activity.
TrpV1 channels also called vanilloid receptors that respond to heat and capsaicin (224) are strongly sensitized by bradykinin and other PLC activators, and it was suggested that PtdIns(4,5)P2 breakdown relieves a tonic inhibition of these channels by PtdIns(4,5)P2 (257). However, the lipid regulation of these channels appears to be more complicated as they need phosphoinositides for their activity, and the effects of PtdIns(4,5)P2 also depend on the extent of stimulation by capsaicin (951, 1286, 1587) or association with other proteins (728, 780) and PtdIns4P may also support their activities (559, 951).