Most significant result of IMPG SAS in 2015 in basic research

19. November 2015
The Scientific Board of IMPG SAS evaluated as the most significant result of 2015 in basic research the work by authors M. Karmažínová, K. Jašková, P. Griač, E. Perez-Reyes, Ľ. Lacinová:

Gating of T-type calcium channels is controlled by the voltage sensor in domain I

Low-voltage calcium channels of the T-type (CaV3.n) have a low activation threshold (about -60 mV) that enables their participation in the initiation of the action potential. It is not clear why they can activate much more easily than the high-voltage calcium channels (HVCCs). Opening of the channel pore, which allows passion of ion currents, is preceded by activation of the voltage sensor that can be measured as the gating current. There are four independent voltage sensors in the structure of voltage-dependent calcium channels, one in each of the four domains of the channel. Accorgind to the classical model, channel opening follows activation of all four voltage sensors. We have shown that in contrast to HVCCs, the voltage dependence gating current amplitude does not precede the voltage dependence of ion current, but crosses it. It means that activation of CaV3.n channels does not require activation of all four voltage sensors. Based on our results we have proposed a hypothesis that the decisive step on T-type channel activation id activation of the voltage sensor in the first domain of the channel. They differ from HVCCs also by the higher effectiveness of coupling between activation of the voltage sensor and opening of the conducting pore of the channel.

Schematic description of the structure of a  CaV3.n channel. Green cylinders represent α-helices of the conducting pored, orange cylinders are the positively charged S4 segments, the movement of which (step 1) corresponds to activation of the voltage sensor and generates the gating current IG. Step 2 represents the resultant opening of the conducting pore, through which the ion current ICa flows.

Project: VEGA 2/0044/13

Publication: KARMAŽÍNOVÁ, MáriaJAŠKOVÁ, Katarína – GRIAČ, Peter – PEREZ-REYES, Edward – LACINOVÁ, Ľubica. Contrasting the roles of the I-II loop gating brake in CaV3.1 and CaV3.3 calcium channels. In Pflugers Archiv-European Journal of Physiology, 2015, vol. 467, no. 12, p. 2519–2527. (4.101 – IF2014). ISSN 0031-6768.