Molecular Determinants of Cav1.2 Calcium Channel Inactivation.

Nikolai M. Soldatov

doi:10.5402/2012/691341

Abstract

Voltage-gated L-type Cav1.2 calcium channels couple membrane depolarization to transient increase in cytoplasmic free Ca2+ concentration that initiates a number of essential cellular functions including cardiac and vascular muscle contraction, gene expression, neuronal plasticity, and exocytosis. Inactivation or spontaneous termination of the calcium current through Cav1.2 is a critical step in regulation of these processes. The pathophysiological significance of this process is manifested in hypertension, heart failure, arrhythmia, and a number of other diseases where acceleration of the calcium current decay should present a benefit function. The central issue of this paper is the inactivation of the Cav1.2 calcium channel mediated by multiple determinants.

Highlights

The voltage-gated inward Ca2+ current (ICa) is a common mechanism of transient increase in the cytoplasmic free Ca2+ concentration triggered by cell depolarization
Using Fluorescent resonance energy transfer GFP (FRET) microscopy combined with patch clamp, we found that inactivation causes strong mutual reorientation of the α1C and β1a NH2termini, but their distance vis-a-vis the plasma membrane is not appreciably changed [19]
This paper has demonstrated that we know how to accelerate inactivation of Cav1.2 to τ f less than 10 ms (Figure 3(C)), to deprive it from inactivation completely (Figures 4(B) and 4(C)), or to eliminate dependence of its expression from β or α2δ without significant consequences for inactivation

Summary

Introduction

The voltage-gated inward Ca2+ current (ICa) is a common mechanism of transient increase in the cytoplasmic free Ca2+ concentration triggered by cell depolarization This form of Ca2+ signaling activates essential cellular processes including cardiac contraction [1], regulation of a smooth muscle tone [2], gene expression [3], synaptic plasticity [4] and exocytosis [5]. Occurring diversity of Cav1.2 complicates the interpretation of data obtained from native cells, let alone the single channel data This underlies the importance of Cav1.2 research in recombinant expression systems where the molecular composition of the channel and the structure of its constituents are predefined.

Plasma membrane

Findings

Conclusions