Channel formation by salmon and human calcitonin in black lipid membranes.
In this study we investigated the interaction of salmon and human calcitonin (Ct) with artificial lipid bilayer membranes. Both peptides were able to form either transient or permanent channels in the model membranes. The channels formed by salmon Ct at concentration (125 nM) had, on average, a single-channel conductance of 0.58 +/- 0.04 nS in 1M KCl (+10 mV), which is voltage-dependent at lower voltages. Human Ct forms at the same concentration channels with a much lower probability, and high voltages of up to +150 mV were needed to initiate channel formation. The estimated single-channel conductance formed under these conditions was approximately 0.0119 +/- 0.0003 nS in 1 M KCl. Both salmon and human Ct channels were found to be permeable to calcium ions. The possibility is discussed that the superior therapeutic effect of salmon Ct as a tool to treat bone disorders, including Paget disease, osteoporosis, and hypercalcemia of malignancy, rather than human Ct is related to the lack of the fibrillating property of salmon Ct. Preliminary data indicate that also eel and porcine Ct and carbocalcitonin form channels in model membranes.
Stipani
V
V
Dept. Farmaco-Biologico, Università degli Studi di Bari, I-70126 Bari, Italy.
Gallucci
E
E
Micelli
S
S
Picciarelli
V
V
Benz
R
R
D000818:Animals; D002116:Calcitonin / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004594:Electrophysiology; D006801:Humans; D007477:Ions; D008051:Lipid Bilayers / Q000378:metabolism*; D012474:Salmon; D012492:Salts / Q000494:pharmacology; D013997:Time Factors
D007477:Ions; D008051:Lipid Bilayers; D012492:Salts; D002116:Calcitonin; D002118:Calcium