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A new class of calcium channels activated by glucose in human pancreatic β‐cells
Author(s) -
Rojas Eduardo,
Hidalgo Jorge,
Carroll Patricia B.,
Li Min Xu,
Atwater Illani
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80568-4
Subject(s) - pipette , biophysics , membrane potential , chemistry , hexokinase , calcium , patch clamp , conductance , beta cell , channel blocker , membrane , diazoxide , calcium channel , electrophysiology , medicine , endocrinology , biochemistry , islet , glycolysis , biology , insulin , enzyme , receptor , mathematics , organic chemistry , combinatorics
Single calcium‐channel currents were recorded from membrane patches of cultured β‐cells dissociated from human islets of Langerhans. In the absence of exogenous glucose, low frequency spontaneous calcium‐channel openings of small amplitude (−0.34 ± 0.02 pA at 0 m V pipet potential) were observed in all membrane patches examined (25 mM Ca 2+ in the patch pipet). The frequency of channel openings was rather insensitive to the membrane potential across the patch (range from ca 0 to 60 m V pipet potential; chord conductance 4.9 ± 0.2 pS). Addition of glucose induced a dose‐dependent increase in the frequency of openings of the Ca 2+ ‐channel (from now on referred to as the Ca G ‐channel). A few minutes after the addition of glucose (⩾ 11 mM), bursts of action potentials were often observed which were elicited only if Ca 2+ was present in the solution bathing the β‐cells. Application of glucose in the presence of mannoheptulose (11 mM), a blocker of the hexokinase controlling the first stage of glycolysis, had no effect and the activity of the Ca G ‐channel remained at its resting level. The readily permeant mitochondrial substrate 2‐ketoisocaproate (KIC, 10 mM) was as effective as glucose in eliciting action potentials from cells forming part of cell aggregates. The activity of the Ca G ‐channel was significantly increased by KIC (11 mM). Although spike and Ca 2+ ‐channel activity were markedly stimulated by glucose or KIC in all cells examined, regular bursts of action potentials were seen only if the patch was formed on β‐cells which were part of a cell aggregate. Mannoheptulose (11 mM) prevented the activation of the Ca G ‐channel by glucose (11 mM) but not by KIC (11 mM). Once activated, the Ca G ‐channel remained active even after excision of the patch. We propose that the physiological control of this Ca 2+ ‐channel is mediated by one or more products of glucose metabolism.