Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvbeta1.1 A-type K+ channels.
Voltage-gated Kv1.1/Kvbeta1.1 A-type channels, as a natural complex, can switch from fast to slow inactivation under oxidation/reduction conditions. The mode-switching of inactivation, which is mediated by a cysteine residue in the inactivation ball domain of the Kvbeta1.1 N terminus, can regulate membrane electrical excitability. In the present study, we identified a mechanism whereby inactivation in Kv1.1/Kvbeta1.1 channels is regulated by calcium influx. The rise in intracellular calcium, due to either influx from extracellular space or release from intracellular stores, eliminates fast inactivation induced by Kvbeta1.1, resulting in slower inactivation and increased steady-state current. This oxidation-independent calcium effect is mediated through the Kvbeta1.1 N terminus, not the C terminus. We propose that a coupling between calcium influx and inactivation of voltage-gated A-type K+ channels occurs as a result of membrane depolarization and may contribute to afterhyperpolarization as negative feedback to control neuronal excitability.
Neuroscience Discovery Research, Wyeth Research, CN-8000, Princeton, NJ 08543, USA.
Flora
F
Jow
Zhi-Hao
ZH
Zhang
David C
DC
Kopsco
Karen C
KC
Carroll
Kewei
K
Wang
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating; D051662:Kv1.1 Potassium Channel; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus
C496946:KCNA1 protein, human; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D000001:Calcimycin; D002118:Calcium