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Laboratory of Molecular Physiology and Neurobiology
Department of Department of Biosciences
University of Milan
Via Celoria 26, 20133
Tel. +39 02.503.14931
Fax +39 02.503.14932

dario.difrancesco@unimi.it

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Laboratory
Laboratory of Molecular Physiology and Neurobiology
Department of Biosciences
University of Milan
Via Celoria 26, 20133
Tel. +39 02.503.14931
Fax +39 02.503.14932

lab

The laboratory of Molecular Physiology and Neurobiology investigates the properties of cardiac ion channels. Our main project concerns the pacemaker ("funny") If current, first described in the pacemaker cells of the sinoatrial node (SAN) (Brown, DiFrancesco & Noble, 1979, Nature 280, 235) and later characterized in cardiac myocytes and neurons.
Cardiac rhythmic activity is generated by "pacemaker" cells, which in mammals are located in the SAN. Action potentials of SAN cells have a special phase, called diastolic (or pacemaker) depolarization: at the end of an action potential, the pacemaker depolarization slowly moves the membrane voltage up to threshold for firing of a new action potential, thus generating repetitive activity. The mechanism responsible for initiation of the process of pacemaker depolarization is the activation during diastole of the pacemaker If current. As well as by voltage hyperpolarization, If is activated by intracellular cAMP, and is therefore modulated by the autonomic neurotransmitters noradrenaline (which activates If by increasing intracellular cAMP, thus accelarating rate) and acetylcholine (which inhibits If by the decreasing intracellular cAMP, thus slowing rate). These mechanisms are therefore responsible for the modulation of cardiac rate by the autonomic nervous system. If-like currents have also been described in a variety of neuronal preparations (Ih). In sensory neurons Ih is involved in the perception of external stimuli, or in modulating the transduction of sensory stimuli into electrical signalling. Ih is also expressed in some pre-synaptic membranes, where it is involved in plasticity phenomena.
Our laboratory uses the most recent techniques of electrophysiology, biochemistry, immunofluorescence, molecular and cellular biology and other.

 

 

 


   
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