HCN function can be studied in human axons in vivo
DavidBurke, Neurologist, Department of Neurology, Royal Prince Alfred Hospital, The University of Sydney, Sydney, N.S.W. 2006david.burke@sydney.edu.au
David Burke, Sydney, Australia; James Howells, Sydney, Australia; Susan E. Tomlinson, Sydney, Australia
Submitted January 29, 2013
Dr. Benarroch highlighted the function of HCN channels. [1] Studies of axonal excitability using threshold tracking techniques allow HCN function to be quantified indirectly in human peripheral nerve in vivo. [2]. These physiological studies can provide insight into the activity of different voltage-dependent channels expressed on the studied axons, even in CNS disease. For example, abnormalities have been documented in benign familial neonatal epilepsy, a condition due to mutation of the KCNQ2 gene encoding Kv7.2. The abnormalities in axonal excitability were those appropriate for loss of slow K+ channel function. [3] Current protocols for studying the accommodation to hyperpolarization produced by HCN currents now use strong long hyperpolarizing currents as conditioning stimuli to alter membrane potential. [4] This has allowed further insight into the nature of HCN current in human myelinated axons, specifically that HCN1 is probably expressed on large myelinated axons, but that isoform expression may differ for myelinated afferent and efferent axons. [5] In defined patient groups with epilepsy, these techniques could help clarify whether there is abnormal HCN function. In neuropathic pain, the situation is less certain because the action potentials of small nociceptive afferents can be characterized only with microneurography.
1. Benarroch EE. HCN channels: Function and clinical implications.
Neurology 2013; 80:304-310.
2. Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the
study of human peripheral nerve. Muscle Nerve 1998;21:137-158.
3. Tomlinson SE, Bostock H, Grinton B, et al. In vivo loss of slow
potassium channel activity in individuals with benign familial neonatal epilepsy in remission. Brain 2012;135:3144-3152.
4. Tomlinson S, Burke D, Hanna M, Koltzenburg M, Bostock H. In vivo
assessment of HCN channel current (Ih) in human motor axons. Muscle Nerve 2010;41:247-256.
5. Howells J, Trevillion L, Bostock H, Burke D. The voltage dependence of
Ih in human myelinated axons. J Physiol 2012;590:1625-1640.
For disclosures, contact the editorial office at journal@neurology.org.
Dr. Benarroch highlighted the function of HCN channels. [1] Studies of axonal excitability using threshold tracking techniques allow HCN function to be quantified indirectly in human peripheral nerve in vivo. [2]. These physiological studies can provide insight into the activity of different voltage-dependent channels expressed on the studied axons, even in CNS disease. For example, abnormalities have been documented in benign familial neonatal epilepsy, a condition due to mutation of the KCNQ2 gene encoding Kv7.2. The abnormalities in axonal excitability were those appropriate for loss of slow K+ channel function. [3] Current protocols for studying the accommodation to hyperpolarization produced by HCN currents now use strong long hyperpolarizing currents as conditioning stimuli to alter membrane potential. [4] This has allowed further insight into the nature of HCN current in human myelinated axons, specifically that HCN1 is probably expressed on large myelinated axons, but that isoform expression may differ for myelinated afferent and efferent axons. [5] In defined patient groups with epilepsy, these techniques could help clarify whether there is abnormal HCN function. In neuropathic pain, the situation is less certain because the action potentials of small nociceptive afferents can be characterized only with microneurography.
1. Benarroch EE. HCN channels: Function and clinical implications. Neurology 2013; 80:304-310.
2. Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve 1998;21:137-158.
3. Tomlinson SE, Bostock H, Grinton B, et al. In vivo loss of slow potassium channel activity in individuals with benign familial neonatal epilepsy in remission. Brain 2012;135:3144-3152.
4. Tomlinson S, Burke D, Hanna M, Koltzenburg M, Bostock H. In vivo assessment of HCN channel current (Ih) in human motor axons. Muscle Nerve 2010;41:247-256.
5. Howells J, Trevillion L, Bostock H, Burke D. The voltage dependence of Ih in human myelinated axons. J Physiol 2012;590:1625-1640.
For disclosures, contact the editorial office at journal@neurology.org.