Can New Insights into Sodium Channels Eventually Curb Prescription Narcotic Addiction ?
Alan Hodgkin
I
have the habit of perusing the newly arrived medical journals , NEJM or Neurology while watching news on the TV . That allows me to filter off boring news and the frequent interruption by commercials . A few weeks ago , I was startled by a piece of news that made me wonder about the depth of human depravity and moral turpitude . It was about the recent incident in which a toddler died of fentanyl toxicity at a preschool recently . It made me wonder who would stoop so low and be stupid enough to hide narcotics in the playroom of preschoolers . By a strange coincidence , I was reading a paper published in the NEJM about a drug that selectively affects the sodium channels of dorsal root ganglia without any effect on the sodium channels of the central nervous system . The thought crossed my mind : If we have several such drugs , there may be no need to prescribe narcotics for pain control after surgical procedures . This is quite relevant because studies have shown that some opioid-naïve patients who are prescribed narcotics for post-surgical pain eventually become addicted to those drugs . 1
The discovery of membrane channels is one of the most fascinating stories of medical science . I can ’ t help sharing an anecdote with you . Sixty years ago , I completed medical school and was getting ready to start internship with the usual pride and excitement of becoming a “ real doctor .” As was the tradition in those days , I set out to meet my professors and personally thank them
by VASUDEVA IYER , MD
Andrew Huxley
for their teaching , which groomed me to be a budding physician . I was fond of my biophysics teacher who even at that time tried to elaborate on ( to a bunch of bored and bewildered medical students ) the principle of voltage clamping . His secretary warned me that the professor was in an unusual mood that day , laughing and sometimes ranting . When he saw me , he proclaimed that he was very glad to see me on this “ most important day .” I thought he was happy that I had finally become a doctor ! But to my chagrin , he added , “ What a pleasant news , my heroes Hodgkin and Huxley won the Nobel prize for their work on electric signal generation and propagation through the nerve .” I was a bit crestfallen but kept a smiling face while he ranted about the techniques the two scientists used in their discovery .
Although the presence of voltage gated sodium channels has been postulated , their role in signal transmission came to light by the collaborative work of Alan Hodgkin and Andrew Huxley . They experimented on the giant axon of squids which can be as big as 1 mm in diameter , allowing insertion of electrode inside the axon . They could keep the membrane potential at a specific voltage ( voltage clamp ) and study the concentration of ions like sodium and potassium . Their work led to the understanding of the generation of the action potential ; sodium ions rush in initially causing the rising phase of the action potential and potassium ions exit terminating the action potential . Bert Sakmann and Erwin Neher developed the patch clamp technique which further advanced knowledge of ion channels , for which they were awarded the Nobel prize in 1991 . The development of gene sequencing and recombinant DNA
20 LOUISVILLE MEDICINE