PubMed 20392696

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Slo1 , Slo3

Title: Phosphatidylinositol 4,5-bisphosphate activates Slo3 currents and its hydrolysis underlies the epidermal growth factor-induced current inhibition.

Authors: Qiong-Yao Tang, Zhe Zhang, Jingsheng Xia, Dejian Ren, Diomedes E Logothetis

Journal, date & volume: J. Biol. Chem., 2010 Jun 18 , 285, 19259-66

PubMed link:

The Slo3 gene encodes a high conductance potassium channel, which is activated by both voltage and intracellular alkalinization. Slo3 is specifically expressed in mammalian sperm cells, where it gives rise to pH-dependent outwardly rectifying K(+) currents. Sperm Slo3 is the main current responsible for the capacitation-induced hyperpolarization, which is required for the ensuing acrosome reaction, an exocytotic process essential for fertilization. Here we show that in intact spermatozoa and in a heterologous expression system, the activation of Slo3 currents is regulated by phosphatidylinositol 4,5-bisphosphate (PIP(2)). Depletion of endogenous PIP(2) in inside-out macropatches from Xenopus oocytes inhibited heterologously expressed Slo3 currents. Whole-cell recordings of sperm Slo3 currents or of Slo3 channels co-expressed in Xenopus oocytes with epidermal growth factor receptor, demonstrated that stimulation by epidermal growth factor (EGF) could inhibit channel activity in a PIP(2)-dependent manner. High concentrations of PIP(2) in the patch pipette not only resulted in a strong increase in sperm Slo3 current density but also prevented the EGF-induced inhibition of this current. Mutation of positively charged residues involved in channel-PIP(2) interactions enhanced the EGF-induced inhibition of Slo3 currents. Overall, our results suggest that PIP(2) is an important regulator for Slo3 activation and that receptor-mediated hydrolysis of PIP(2) leads to inhibition of Slo3 currents both in native and heterologous expression systems.