KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels

Our laboratory previously cloned a novel rabbit gene (Kcn1), expressed in k idney, heart, and aorta, and predicted to encode a protein with 58% amino a cid identity with the K channel Shaker Kv1.3 (Yao X et al. Proc Natl Acad S ci USA 92: 11711-11715, 1995). Because Kcn1 did not express well (peak curr ent in Xenopus laevis oocytes of 0.3 mu A at +60 mV), the human homolog (KC NA10) was isolated, and its expression was optimized in oocytes. KCNA10 med iates voltage-gated K+ currents that exhibit minimal steady-state inactivat ion. Ensemble currents of 5-10 mu A at +40 mV were consistently recorded fr om injected oocytes. Channels are closed at the holding potential of -80 mV but are progressively activated by depolarizations more positive than -30 mV, with half-activation at +3.5 +/- 2.5 mV. The channel displays an unusua l inhibitor profile because, in addition to being blocked by classical K ch annel blockers (barium tetraethylammonium and 4-aminopyridine), it is also sensitive to inhibitors of cyclic nucleotide-gated (CNG) cation channels (v erapamil and pimozide). Tail-current analysis shows a reversal potential sh ift of 47 mV/decade change in K concentration, indicating a K-to-Na selecti vity ratio of at least 15:1. The phorbol ester phorbol 12-myristate 13-acet ate, an activator of protein kinase C, inhibited whole cell current by 42%. Analysis of single-channel currents reveals a conductance of similar to 11 pS. We conclude KCNA10 is a novel human voltage-gated K channel with featu res common to both K-selective and CNG cation channels. Given its distribut ion in renal blood vessels and heart, we speculate that KCNA10 may be invol ved in regulating the tone of renal vascular smooth muscle and may also par ticipate in the cardiac action potential.