Short Presentation

Cells composing living bodies are equipped with many machineries to maintain independence from the external environment. In addition, cells are also prepared to respond to stimulation from extracellular milieu. Needless to say, intracellular and extracellular media are solution containing inorganic ions. Intracellular concentrations of Na+, K+, Ca²⁺ and Cl- are not equal to those on the extracellular side, and fluctuate in response to various stimuli from the external milieu.

This ambivalence in regard to the relationship with the extracellular environment is a distinctive feature of living cells. Ion channels (pore on plasma membrane carrying ions), transporters and pumps (transporting various substances including inorganic ions) play important roles to control dependence or independence of living cells on extracellular environment. In this division, we focus on ion channels.

Among various inorganic ions, Ca²⁺ is particularly important triggering diverse biological functions such as muscle contraction and neurotransmitter release.Ca²⁺ is known to regulate cellular HOMEostasis such as cell proliferation, survival and death as well. Intracellular Ca²⁺ concentration is quite low before stimulation (nM levels), but once cells are stimulated, it increases to mM levels. How does Ca²⁺ influx occur in the Ca²⁺ cellular responses to increase intracellular Ca²⁺ concentration? Now it is believed that influx occurs via Ca²⁺ channel across plasma membrane from extracellular media where extracellular Ca²⁺ concentration is 1-2 mM. Ca²⁺ channels are diverse, including voltage-dependent Ca²⁺ channels gated by electrical potential difference across the plasma membrane, and receptor-mediated Ca²⁺ channels activated by inositol metabolites and other cellular messengers.

Do you know "reactive oxygen species"? These reactive chemical substances are composed of oxygen, and generally thought to mediate cytotoxicity, cytoclasis and cell death. "Antioxidants", which are recently receiving great attention, are effective to neutralize and detoxify reactive oxygen species. However, it is known that reactive oxygen species are important not only for these negative aspects, but also for cellular HOMEostasis such as differentiation and proliferation. Similar Ca²⁺ to and inositol metabolites, reactive oxygen species are physiologically active substances that have bilateral character.

In order to clarify the nature of physiological responses, we focus on voltage-dependent Ca²⁺ channels and receptor-mediated TRP channels, and study how ion channels are encoded as genetic information. Furthermore, we investigate how ion channels are activated and function in response to the stimulation from extracellular environment.