Effects of Cavβ3 mutations on 4-AP–induced potentiation of N-type and L-type Ca2+ channels in HEK293 cells
n = 6–8 cells in each group; data are expressed as means ± S.E.M.
| Mutant | Mutation Sites | N-type | L-type | Basal IBa | ||
|---|---|---|---|---|---|---|
| % Increase in IBa | Basal IBa | % Increase in IBa | ||||
| (3 mM 4-AP) | (0.3 mM 4-AP) | (1 mM 4-AP) | ||||
| pA | pA | |||||
| Cavβ3 (wild-type) | 183.9 ± 34.4% | 786.5 ± 180.2 | 122.5 ± 22.4% | 250.5 ± 20.8% | 389.1 ± 91.5 | |
| Cavβ2 (wild-type) | 77.7 ± 22.9% | 748.1 ± 51.8 | 11.1 ± 3.8% | 46.6 ± 21.4% | 333.4 ± 13.8 | |
| Cavβ3-A1 (M195-M196) | MM → AA | No effect | 15.8 ± 8.4 ** | 50.7 ± 5.5% * | 52.5 ± 8.6% * | 45.5 ± 13.9 ** |
| Cavβ3-A2 (K198-L200) | KAL→ AGA | 99.8 ± 15.8% * | 651.7 ± 110.4 | No effect | No effect | 645.8 ± 93.0 |
| Cavβ3-A3 (V292-S295) | VKVS → AKAA | No currents | No currents | No currents | No currents | No currents |
| Cavβ3-A4 (V299-L303) | VLQRL → ALQAA | No effect | 33.3 ± 13.1 ** | No currents | No currents | No currents |
| Cavβ3-A5 (L337-N340) | LDEN → ADAA | 66.2 ± 10.5% * | 42.8 ± 9.2 ** | No currents | No currents | No currents |
| Cavβ3-A6 (L342-A345) | LDDA → ADDG | No currents | No currents | 5.13 ± 2.5% ** | 23.8 ± 4.6% ** | 248.2 ± 198.7 |
| Cavβ3-P1 (K134-G148) | KARRSGNPSSLSDIG (Cavβ3) | 71.9 ± 19.6% * | 661.8 ± 137.9 | 15.6 ± 5.6% ** | 54.9 ± 3.5% * | 583.3 ± 210.4 |
| →RAKQGKFYSSKSGGNSSSSLGDIVPS (Cavβ2) | ||||||
| Cavβ3-P1a (K134-R137) | KARR → AAAA | No currents | No currents | No effect | No effect | 316.5 ± 93.4 |
| Cavβ3-P1b (S138-P141) | SGNP → AAAA | 18.3 ± 5.1% ** | 138.2 ± 37.9 ** | No currents | No currents | No currents |
| Cavβ3-P1c (S142-S145) | SSLS → AAAA | 214.5 ± 50.6% | 690.8 ± 93.0 | No currents | No currents | No currents |
| Cavβ3-P1d (D146-G148) | DIG → AAA | 45.8 ± 31.3% * | 722.1 ± 110.5 | 14.0 ± 2.8% ** | 52.8 ± 23.5% * | 289.4 ± 140.4 |
| Cavβ3-P1-D146 | D → A | 167.2 ± 35.4% | 628.8 ± 125.5 | 15.0 ± 3.5% ** | 52.5 ± 11.3% * | 245.1 ± 58.9 |
| Cavβ3-P1-I147 | I → A | No currents | No currents | 55.2 ± 20.8% * | 64.1 ± 3.5% * | 307.7 ± 76.2 |
| Cavβ3-P1-G148 | G → A | No currents | No currents | 4.17 ± 1.5% ** | 193.7 ± 2.9% | 222.8 ± 88.7 |
| Cavβ3-P2 (ins P367) | (ins) PNPLLSRT (Cavβ2) | 60.2 ± 8.3% * | 750.8 ± 131.8 | 20.8 ± 11.3% ** | 78.3 ± 2.3% * | 625.9 ± 97.5 |
| Cavβ3-P3 (ins G368) | (ins) ATST (Cavβ2) | No currents | No currents | No currents | No currents | No currents |
| Cavβ3-P4 (ins E480) | (ins) PVKKSQHRSSSATH (Cavβ2) | 148.9 ± 20.5% | 850.4 ± 179.2 | No effect | No effect | 598.6 ± 154.3 |
↵* P < 0.05, **P < 0.01, compared with the Cavβ3 wide-type controls (repeated measures analysis of variance followed by Dunnett’s post hoc test).