My Thesis
My PhD thesis entitled “Functional and Structural Studies of the Human Voltage-Gated Proton Channel” has recently been published online by the Rockefeller University website here. The Thesis covers six years of extensive research that I carried out in the Laboratory of Molecular Neurobiology and Biophysics at the Rockefeller University under the tutelage of Dr Roderick MacKinnon. … Continue reading
Omega Current Channelopathies
In this post I will be continuing my series on the omega current. The omega current is a leak current that passes through the voltage-sensor domain (VSD) of mutated voltage-gated cation channels. Mutation of the VSD S4 helix can reveal a cryptic pore that allows ions (H+, Li+, K+, Rb+ and even guanidinium) to cross … Continue reading
The Omega Current
Mutation of voltage-sensor domains (VSDs) can sometimes lead to ions leaking across the membrane through the VSDs themselves. Ion conduction through the mutated VSD of the Shaker Kv channel was coined the “omega current” by Tombola, Pathak and Isacoff (Tombola et al., 2005). Many different mutations have been identified that result in current leaking through the VSDs of … Continue reading
Pores and Selectivity Filters
In this post I will be briefly introducing the classical ideas of ion conduction through membrane proteins. The idea of ion channels as selective pores in the cell membrane is very old but is now understood at atomic detail. So what is a channel? What does an ion conductive pore look like? Here, I will … Continue reading
Hv Physiology: Breast Cancer
In this post I will discuss the role of human Hv1 channels in promoting the pathology and invasiveness of breast cancers. It is well known that cancer consists of normal cells gone awry. As cells age, they can accumulate mutations in their genomes and sometimes these mutations lead to unregulated growth and expansion. The unregulated, … Continue reading
Hv Physiology: Brain Damage
Thanks to the groundbreaking work of Hodgking and Huxley, the most well known physiological role of voltage-gated ion channels is the propagation of the action potential in neurons (Hodgkin & Huxley, 1952). What Hodgkin and Huxley demonstrated was that the action potential is generated by the sequential opening and closing of voltage-gated Na+ and K+ … Continue reading
Hv Physiology: Human Male Fertility
The human voltage-gated proton channel Hv1 plays an important physiological role in male fertility in humans. Specifically it is integral for regulation of the internal pH of the sperm cell. The pH of the sperm cytoplasm is a major regulator of sperm cell motility, capacitation, hyperctivation and the acrosome reaction. Each of these processes are … Continue reading
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