**7. Conclusion**

In summary, Maxi anion and pl-VDAC had unitary conductance of 400 pS, but were voltage-dependent and anionic. In relation to Maitotoxin and TRPV1 pores which were not

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A better understanding of the molecular mechanism for P2X7 pore formation might open new therapeutic strategies since this receptor is involved in several processes such as the killing of intracellular pathogens, chronic inflammation, neuropathic pain and rheumatoid arthritis.

So, despite the important efforts carried out in the studies of P2X7 receptor, the pore opening mechanism (large channel) is still unknown.

#### **8. References**


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**3** 

*Czech Republic* 

**Facilitation of Neurotransmitter and Hormone** 

Nucleotides are emerging as ubiquitous family of extracellular signaling molecules. Their effects are mediated through a specific class of plasma membrane receptors called purinergic P2 receptors that, according to the molecular structure, are further subdivided into two subfamilies: P2Y and P2X. Specifically, P2X receptors (P2XRs) are ligand-gated ion channels, whereas P2Y receptors (P2YRs) belong to the superfamily of G-protein-coupled

Purinergic P2XRs are expressed in a wide range of organisms from amoeba to humans (Fountain et al., 2007). In mammals, seven P2X subunits (termed P2X1-7) have been found (North, 2002). These receptors appeared early in evolution and have a widespread distribution on many neurons and non-neuronal cells. The P2XRs comprise the family of trimeric channels that use the energy of extracellular ATP binding to initiate a depolarizing flux of cations, including calcium, through the pore of channels. The extracellular actions of ATP are terminated by ectonucleotidases, leading to the generation of ADP, a primary agonist for some P2YRs, and adenosine, the common agonist for adenosine subtypes of receptor (Ralevic and Burnstock, 1998). Substantial progress has been made in elucidating the roles these receptors play under physiological and pathological conditions and in our understanding of the functional, structural, and pharmacological properties of seven P2X receptor subtypes. Purinergic signaling is involved in several basic physiological responses such as embryonic and stem cell development, pain sensation, regulation of renal blood flow, inflammatory responses, auditory neurotransmission etc., whereas pathophysiology of purinergic signalling includes stroke, thrombosis, osteoporosis, kidney failure, bladder incontinence, cystic fibrosis, dry eye, cancer and brain disorders (Khakh and North, 2006; Surprenant and North, 2009; Burnstock, 2011). In excitable cells, P2XR activation causes an increase in the cytosolic Ca2+ concentration via two distinct mechanisms: by membrane depolarization resulting in voltage-dependent Ca2+ entry and by Ca2+ entry through the P2XR itself. The role of P2XR involves fast synaptic transmission mediated by ATP in both the peripheral (Evans et al., 1992) and central nervous systems (Edwards et al., 1992), modulation of neuronal excitability (Khakh and Henderson, 1998), long-term potentiation (Sim et al., 2006), and stimulation of hormone secretion (luteinizing hormone, prolactin, oxytocin and vasopressin) (Kapoor and Sladek, 2000; Stojilkovic, 2009; Stojilkovic et al.,

**1. Introduction** 

receptors.

**Release by P2X Purinergic Receptors** 

*Institute of Physiology of the Academy of Sciences of the Czech Republic,* 

Vojtech Vavra, Anirban Bhattacharya, Marie Jindrichova and Hana Zemkova

